PATHOLOGY  OF  THE  NERVOUS  SYSTEM 


PATHOLOGY  OF  THE 

NERVOUS     SYSTEM 


E.   FARQUHAR  ^UZZARD 

M.A.,  M.D.,  F.R.C.P. 

PHYSICIAN    TO    ST.    THOMAS'S    HOSPITAL 

AND    PHYSICIAN    TO    OUTPATIENTS    AT    THE    NATIONAL    HOSPITAL    FOR    THE 

PARALYSED    AND    EPILEPTIC 

AND 

J.   GODWIN   GREENFIELD 

B.Sc,  M.D.,  M.R.C.P. 

i^VVTHOLOGIST    TO    THE    NATIONAL    HOSPITAL    FOR    THE    PARALYSED 
AND    EPILEPTIC 


PAUL   B.   HOEBER 

67    &    69    EAST    59TH    STREET 

NEW  YORK 

1922 


»    c      •      e 


.  •   .  r    .^     •  e^ 


PRINTED    IN   GREAT    BRITAIN    BY 
ILLING    AND    SONS,    LTD.,    GUILDFORD    AND    ESHER 


PREFACE 

In  offering  this  volume  to  medical  students  and  practitioners 
the  authors  believe  that  they  are  meeting  a  real  need.  They 
have  attempted  to  describe  clearly  the  anatomical  changes 
which  are  associated  with  disorders  of  nervous  function,  to 
discuss  briefly  questions  of  pathogenesis,  and  to  indicate  in  a 
few  words,  where  it  is  possible,  the  relationship  between 
structural  alterations  and  clinical  signs  and  symptoms.  It 
may  be  true  that  further  advances  in  our  knowledge  of  nervous 
diseases  must  depend  on  the  study  of  function  and  disorders 
of  function  more  than  on  the  consideration  of  advanced 
structural  defects,  but  scientific  speculation  in  regard  to  the 
former  must  always  be  tempered  by  acquaintance  with  the 
latter.  No  student  of  neurology  or  of  psychiatry  can  be  fully 
equipped  for  his  work  unless  he  has  spent  time  and  energy  in 
a  neuro-pathological  laboratory,  and  the  object  of  this  book 
will  be  achieved  if  it  serves  to  economise  his  time  and  to  guide 
his  energy. 

The  authors  are  conscious  of  the  debt  they  owe  to  the 
Board  of  Management  and  Medical  Staff  of  the  National 
Hospital  for  the  Paralysed  and  Epileptic  for  the  opportunities 
of  working  in  the  laboratory  of  that  institution. 


480661 


CONTENTS 


CHAPTER  I 
GENERAL  PATHOLOGY 

PAGE 

Introduction             ...             .             .  .         i 

The  Neuron               ...              .              .  .2 

{a)   The  Nerve  Cell             .              .              .             " .  .4 

(6)   The  Nerve  Fibre          .              .              .              .  .14 

The  Neuroglia         .              .              .              .              .  .18 

Paths  of  Infection  in  the  Central  Nervous  System  .       24 

The  Cerebro-spinal  Fluid                .              .              .  •       30 


CHAPTER  II 
DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

1.  Developmental  Diseases     .... 

2.  Birth  Injuries  ..... 

3.  Familial  and  Congenital  Diseases         .    . 

(i.)   Cerebral  and  Myelopathic        .  .  . 

[a]  Amaurotic  family  idiocy 

(6)  Werdnig-Hoffraann  paralysis        . 

(c)  Friedreich's  ataxia 

{d)  Progressive  lenticular  degeneration 

{e)  Huntington's  chorea 

(ii.)  Neural  .  . 

(/)  Peroneal  atrophy 

[g)  Progressive   hypertrophic  interstitial   neuritis 
children  .  .         .     .         .     . 

(iii.)  Myopathic    .  .  .  .  . 

[h)  Family  periodic  paralysis  .     . 

[i)  Myotonia  .... 

(/)  Myotonia  atrophica  .         .      . 

=,  '  {k)  Myopathy 

*  E  (/)  Amyotonia  congenita        .  .  . 


ol 


50 

58 

58 

58 

58 
62 

63 
66 
68 

70 

70 

71 

73 

73 
74 
75 
75 

78 


VIU 


CONTENTS 


CHAPTER  III 
INJURIES  TO  THE  NERVOUS  SYSTEM 

1.  Injuries  to  the  Brain  and  its  Coverings 

2.  Injuries  to  the  Spinal  Cord — Caisson  Disease     . 

3.  Injuries  to  Nerves  .... 


81 
87 
94 


CHAPTER  IV 

CIRCULATORY  DISTURBANCES  OF  THE  BRAIN  AND 
SPINAL  CORD 

IscHAEMic  Softening  of  the  Brain 

Cerebral  Haemorrhage 

Aneurysms  of  the  Cerebral  Arteries 

False  Porencephaly 

Meningeal  Haemorrhage    . 

(a)  Subarachnoid  haemorrhage     . 


{b)  Subdural     haemorrhage. 

rhagica  interna 
(c)  Extradural  haemorrhage 

6.  Sinus  Thrombosis     . 

7.  Haematomyelia 

8.  Haematorrhachis     . 


Pachymeningitis 


haemor 


105 
117 
120 
121 
121 
122 

122 
123 

124 

125 

127 


CHAPTER  V 
SYPHILIS  OF  THE  NERVOUS  SYSTEM 

GUMMATA  ....... 

Gummatous     Meningitis.       Pachymeningitis     Cervicalis 

Hypertrophica 
Gummatous  Arteritis 
Syphilitic  Myelitis 
Tabes  Dorsalis 
General  Paralysis  of  the  Insane 


133 

135 
138 
141 

145 
154 


CHAPTER  VI 
OTHER  INFECTIVE  DISEASES 

1.  Leprosy       .......     160 

2.  Streptothrix  Infection     .  .  .  .  .163 

3.  Tuberculosis  ......     163 

{a)  Tuberculosis   of    the   cranium,    vertebrae,    and    dura 

mater  ......      164 

{b)  Tubercular  leptomeningitis     ....      167 

(c)  Tuberculomata  of  the  brain  and  spinal  cord    ,  .169 


CONTENTS 


IX 


lO. 

II. 

12. 

13- 
14. 

15- 


Acute  Leptomeningitis      .... 

(a)  Meningococcal  meningitis 

(b)  Meningitis  due  to  other  pyogenic  micro-organisms 

(c)  Serous  meningitis  and  meningism 

Pyogenic  Pachymeningitis 

Suppurative    Encephalitis    and   Myelitis    (Abscess 

Brain  and  Spinal  Cord) 
Acute  Myelitis 
Tetanus 


OF 


Acute  Poliomyelitis  and 
Lethargic  Encephalitis 
Landry's  Paralysis 
Herpes  Zoster 
Chorea 

Trypanosomiasis     . 
Hydrophobia  or  Rabies 


Polio-encephalitis 


PAGE 

176 

177 


179 
184 

188 

193 
202 
209 
212 
214 
216 
217 


CHAPTER  VII 

EFFECTS  OF  POISONS 
Neuritis        ...... 

Toxic  Myelitis         ..... 

Encephalopathy  (Effects  of  Poisons  on  the  Brain) 
Ergotism       .  .  .  . 

Pellagra       ...... 

Lathyrism     ...... 

Beri-beri       . 


222 
226 
227 
229 
230 
232 
234 


CHAPTER  VIII 

TUMOURS  OF  THE  BRAIN  AND  SPINAL  CORD 

Tumours  of  the  Brain  and  its  Envelopes 
Glioma — Ependymal  glioma 
Neuroblastoma     . 
Neuro-fibroma 
Carcinoma 
Angeioma 

Sarcoma — Perivascular  sarcoma  . 
Cylindroma 
Endothelioma 
Psammoma 
Cholesteatoma 
Pituitary  tumours 
Pineal  tumours    . 
Dermoid,  parasitic  and  other  cjrsts 
General  pathology  of  intracranial  timiours 


239 
240 
246 
247 
249 
249 
250 
252 

253 
256 
256 
256 

258 
258 
260 


CONTENTS 


B.  Spinal  Tumours       .... 

1.  Tumours  of  the  Envelopes  of  the  Cord 

(a)  Vertebral 

(6)  Intra  vertebral     . 

2.  Intramedullary  Tumours     . 

3.  The  Pathology  of  Spinal  Compression 


264 
264 

264 
266 

267 

269 


CHAPTER  IX 
DISEASES  OF  OBSCURE  ORIGIN 

1.  Motor  Neuron  Disease       .  . 

2.  Subacute  Combined  Degeneration  of  the  Spinal  Cord 

3.  Disseminated  Sclerosis       .... 

4.  Syringomyelia 

5.  Paralysis  Agitans   .  .  ,  .  . 


6.  Myasthenia  Gravis. 


271 
277 
283 
290 
298 
299 


Staining  Methods 


APPENDIX  I 


305 


APPENDIX  II 
Methods  of  Examination  of  the  Cerebro-Spinal  Fluid 

Index    .  .  .  .  . 


322 
327 


LIST  OF  ILLUSTRATIONS 


FIG. 


1.  (a)  Normal  cells  from  hypoglossal  nucleus     .  .  -5 
{b)  Normal  cell  from  ventral  horn  of  lumbar  enlargement  of 

spinal  cord        ...  .  .  .5 

(c)   Pigmentation  of  ventral  horn  cells  .  .  •  5 

2.  Ventral  horn  cells  showing  changes  resulting  from  destruction 

of  ventral  roots  ("  reaction  a  distance  ")  .  .  7 

3.  Ventral   horn    cells    from    a    patient    dying   from    alcoholic 

neuritis  showing  much  vacuolation        .  .  .8 

4.  A    single    nerve    fibre    undergoing    Wallerian    degeneration 

stained  by  the  Marchi  method  .  .  .  .16 

5.  Enlarged  neuroglia  cells  in  the  lateral  columns  of  the  cord 

underlying  a  tumour     .  .  .  .  .21 

6.  Neuroglial  thickening  in  an  old  focus  of  softening  in  the  cere- 

bellum. (From  preparation  stained  by  Professor 
Carl  Weigert,  through  the  kindness  of  Dr.  Gordon 
Holmes)  .  .  .  .  .  .22 

7.  Section  from  spinal  cord  showing  many  corpora  amylacea      .       23 

8.  Normal  choroid  plexus  from  fourth  ventricle .  .  .       30 

9.  Retarded    development    of    brain    from    a    diplegic    infant 

eighteen  months  old      .  .  .  .  '53 

10.  Cerebral  asymmetry  of  congenital  origin  .  .  .54 

11.  Brain  from  case  of  diplegia  showing  shrunken  convolutions 

and  patches  of  cortical  degeneration     .  .  •       55 

12.  Hydromyelus  of  cervical  cord  .  .  .  -57 

13.  {a)  Cells  from  dorsal  horn  and  Clarke's  column  in  a  case  of 

amaurotic  family  idiocy  .  .  .  .60 

(6)  Pur  kin  je  cells  from  the  same  case  .  .  .60 

14.  Three  sections  from  a  case  of  Friedreich's  ataxy  stained  by 

the  Weigert -Pal  method  .  .  .  .65 

15.  Section  of  muscle  from  a  case  of  peroneal  atrophy       .  .71 

16.  Muscle  in  the  pseudo -hypertrophic  form  of  myopathy  .        77 

17.  Sections  stained  by  the  Marchi  method  illustrating  the  ascend- 

ing degeneration  in  the  spinal  cord  following  a  fracture- 
dislocation  in  the  mid-thoracic  region    .  .  .92 

18.  A  peripheral  nerve  undergoing  degeneration  as  the  result  of 

pressure,  stained  by  the  Marchi  method  .  '95 


xii  LIST  OF  ILLUSTRATIONS 

FIG  PAGE 

19.  {a)  A  low-power  photograph  of  an  excised  portion  of  nerve 

which  had  undergone  changes  of  a  fibrotic  character 
following  the  passage  of  a  bullet  through  the  tissues  in  its 
immediate  vicinity.  Photograph  of  sections  taken 
{b)  just  above  and  (c)  below  the  site  of  injury  stained 
by  the  Bielschowsky  method    .  .  .  .96 

20.  Sections  of  ulnar  nerve  seven  months  after  a  wound  that 

severed  it.     Stained  by  the  Weigert-Pal  method  .       98 

2 1 .  Sections  of  an  ulnar  nerve  five  months  after  section  by  wound, 

stained  by  Bielschowsky's  method        .  .  .99 

22.  Cerebral    softening,    the    result    of    embolism    of    the    left 

middle  cerebral  artery,  in  a  case  of  aortic  valvular 
disease  ......     106 

23.  Thrombosis  of  the  left  posterior  cerebral  artery  .  .107 

24.  Softening  in  the  region  of  the  lenticular  nucleus         .  .      108 

25.  Pontine  thrombosis  due  to  disease  of  the  basilar  artery  or  its 

branches  .  .  .  .  .  .      108 

26.  Cerebral  thrombosis  .  .  .  .  .  .109 

27.  Photographs  of  a   brain  illustrating  the  appearances   pro- 

duced by  vascular  lesions  of  varying  severity  .  .111 

28.  Softened  cortex  resulting  from  arterial  thrombosis,  showing 

granular  corpuscles  and  necrotic  pyramidal  cells. 
(Stained  by  haematoxylin  and  van  Gieson)      .  .112 

29.  Fat-laden  granular  corpuscles  in  an  area  of  cerebral  soften- 

ing, the  result  of  embolism  of  a  cerebral  artery 
(Haematoxylin  and  van  Gieson)  .  .  .112 

30.  Softened    brain    tissue    with   fat-laden    granular    corpuscles 

stained  by  the  Marchi  method  .  .  •      113 

31.  Degeneration  of  the  pyramidal  tract  due  to  softening  of  the 

internal    capsule;    stained    by    the    Marchi    method: 

{a)  decussation  of  pyramid ;  (6)  thoracic  cord  .  •      115 

32.  Four  sections  from  a  case  of  pontine  thrombosis  illustrating 

the  secondary  degeneration  in  the  pyramidal  tract: 
{a)  decussation  of  pyramid;  [b]  cervical  enlargement; 
(c)  thoracic  region;  {d)  lumbo-sacral  enlargement 
(Weigert-Pal)   .  .  .  .  .  .116 

33.  Haemorrhage  from  the   anterior   cerebral  artery  ploughing 

up  the  frontal  lobe       .  .  .  .  .117 

34.  Three  photographs  from  a  case  of  cerebral  haemorrhage  with 

extravasation  of  blood  into  the  ventricles  and  minor 
haemorrhages  in  the  pons  .  .  .  .119 

35.  Section    of    optic    nerve    in    secondary    syphilis,    showing 

enormous  infiltration  of  Virchow-Robin  space  with 
mononuclear  cells,  and  glial  overgrowth  in  the  optic 
nerve    .  .  .  .  .  .  .     131 

36.  Drawing  of  a  section  of  the  lumbar  enlargement,  showing  an 

intramedullary  gumma  undergoing  central  caseation    .      132 

37.  Two  sections  through  the  brain  of  a  patient  with  extensive 

gummatous  meningitis  and  meningo-encephalitis         .      134 

38.  A  section  from  sclerosed  area  of  brain  underlying  the  gum- 

matous meningitis  shown  in  fig.  37,  and  showing 
proliferation  and  enlargement  of  neuroglial  cells  .     135 


LIST  OF  ILLUSTRATIONS  xiii 

FIG  PAGE 

39.  {a)  Gummatous  arteritis  of  the  right  middle  cerebral  artery 

with  organisation  of  the  central  clot     .  .  -139 

(b)  The  area  of  softening  in  the  right  hemisphere  resulting 

from  the  arterial  thrombosis     .  .  .  .139 

40.  {a)  Gummatous  arteritis  of  the  anterior  spinal  artery  in  a  case 

of  syphilitic  meningo-myelitis  ....      140 
(6)   Section  of  cord  from  the  same  case  .  .  .140 

41.  Two    sections   illustrating   the   degeneration   in    the    dorsal 

columns  in  tabes  dorsalis  (Weigert-Pal)  .  •      151 

42.  Section   from   prae-Rolandic   cortex  in    a    case    of    general 

paralysis  of  the  insane  .  .  .  .156 

43.  Section  of  first  lumbar  segment  in  a  case  of  general  paralysis 

of  the  insane,  showing  degeneration  in  lateral  columns     157 

44.  Section  from  lumbar  cord  in  a  case  of  taboparesis       .  .157 

45.  Leprosy  bacilli  in  a  dorsal  root  ganglion  cell  .  .  .     162 

46.  Caries  of  lumbar  vertebrae     .  .  .  .  .166 

47.  Section  of  a  vessel  on  the  cerebral  cortex  the  seat  of  tuber- 

cular arteritis  .  .  .  .  .  .169 

48.  Photograph    of    a    section    from     the    medulla    oblongata, 

showing  a  tuberculoma  lying  dorsal  to  one  olive  .      170 

49.  Post-basic  meningitis  .  .  ,  .  .174 

50.  Right  temporo-sphenoidal  abscess  secondary  to  middle-ear 

disease  ......      181 

51.  Bilateral  abscesses  in  frontal  lobes  secondary  to  sphenoidal 

sinusitis  ......      181 

52.  Cavity  in  left  cerebellar  lobe,  the  result  of  an  abscess  secondary 

to  middle-ear  disease    .  .  .  .  .181 

53.  Section  from  the   wall  of  a   cerebral  abscess,  showing  the 

formation  of  fibrous  tissue  and  numerous  granular 
corpuscles         .  .  .  .  .  .183 

54.  Acute  poliomyelitis:   {a)  Section  from  high  thoracic  region 

stained  by  haematoxylin  and  van  Gieson  to  show  the 
cellular  infiltration  of  the  perivascular  spaces  and  of  the 
grey  matter;  {b)  a  higher  power  photograph  of  one  side  of 
the  same  section  .  .  .  .  •     195 

55.  Acute  poliomyelitis.     Photograph  showing  the  meningeal  and 

perivascular  cellular  infiltration  in  the  ventral  fissure  .     196 

56.  Acute  poliomyelitis.     Ventral  horn  cell  preserving  a   fairly 

healthy  appearance  and  surrounded  by  intense  small- 
celled  infiltration  .  .  .  .  .197 

57.  Acute   poliomyelitis.     Two  ventral   horn   cells   undergoing 

destruction  in  the  midst  of  serous  and  cellular  exudation     198 

58.  Acute  poliomyelitis.     Changes  in  the  cells  of  Clarke's  column 

and  surrounding  cellular  infiltration       .  .  -199 

59.  Acute  poliomyelitis.     Section  of  spinal  cord  showing  softened 

area  with  granular  corpuscles,  perivascular  infiltration 
and  haemorrhage  .....     200 

60.  Lethargic  encephalitis.     Cortex  ....     204 

61.  Lethargic  encephalitis.     Cortex  ....     204 

62.  Lethargic  encephalitis.     View  of  longitudinal  section  of  a 

small  blood  vessel  in  the  cortex  .        •      .  .     205 


xiv  LIST  OF  ILLUSTRATIONS 


PAGE 


63.  Lethargic  encephalitis.     Cortex         .             ,             .             .  206 

64.  Lethargic  encephalitis.     View  of  cortex  and  meninges            .  206 

65.  Lethargic  encephalitis.     Blood  vessel  in  medulla       .              .  208 

66.  Lethargic  encephalitis.     Medium-sized  artery  on  the  cortex 

partially  obstructed  with  haemorrhage  in  its  walls,  and 

leading  to  small  wedge-shaped  area  of  infarction            .  208 

67.  Landry's  paralysis     .  .  .  .  .  .211 

68.  The  cord  in  a  case  of  lathyrism  stained  by  the  Weigert-Pal 

method             ......  233 

69.  Glioma  in  parieto-occipital  region  seen  on  the  mesial  surface 

of  the  left  hemisphere  .  .  .  .  .241 

70.  Glioma  of  corpus  callosum  with  numerous  haemorrhages       .  241 

71.  Cystic  glioma  of  left  frontal  lobe        ....  242 

72.  Glioma  of  a  rather  fibrous  type  (microscopic  section)               .  243 

73.  Diffuse  glioma  of  pons  (hypertrophy  of  pons)               .              .  243 

74.  Diffuse  glioma  of  brain-stem  (sagittal  section)             .              .  244 

75.  Glioma  of  pons  invading  fourth  ventricle       .              .              .  244 

76.  Glioma  pontis  (microscopic  section)  ....  245 

77.  Ganglio -neuroma.     High-power  view  of   ganglion   cell   area 

(Bielschowsky's  stain)                ....  247 

78.  Neuro-fibroma  of  acoustic  nerve         ....  248 

79.  Acoustic  nerve  tumour,  showing  "  palisade  "  arrangement  of 

nuclei  (microscopic  section)       ....  249 

80.  Secondary  carcinoma  in  the  cerebral  peduncles  .  .250 

81.  Perivascular  sarcoma.     High-power  view  of  small  vessel       .  251 

82.  Cylindroma  (microscopic  section)       ....  253 

83.  Endothelioma  growing  from  falx  cerebri         .              .              .  254 

84.  Nodular  endothelioma  removed  by  operation .              .              .  254 

85.  Endothelioma  of  dura  (microscopic  section)  .              .              .  255 

86.  Pituitary  tumour       ......  257 

87.  Dermoid  cyst              ......  258 

88.  Colloid  tumour  of  third  ventricle,  possibly  derived  from  the 

pituitary           ......  259 

89.  Hydrocephalus  produced  by  pontine  tumour  .              .              .  261 

90.  A  pressure-cone          .              .              .              .              .              .  262 

91.  Sarcoma  of  cord          ......  267 

92.  Neuro -fibromatosis  of  cauda  equina  ....  268 

93.  Amyotrophic  lateral  sclerosis.     Section  from  the  cervical  en- 

largement        .  .  .  .  .  '273 

94.  Muscles  in  amyotrophic  lateral  sclerosis :  [a)  Early  degenera- 

tion of  muscles;  {b)  advanced  atrophy  of  muscle,  the 

muscle  spindles  escaping           .              .              .              .  2.j^ 

95.  Amyotrophic  lateral  sclerosis.     Longitudinal  section  of  atro- 

phied muscle  fibre         .  .  .  .  .276 

96.  Subacute  combined  degeneration  of   cord.      Three  sections 

representing  the  changes  seen  in  the  cervical,  thoracic 
and     lumbar     regions    stained     by    the    Weigert-Pal 

method              ......  279 


LIST  OF  ILLUSTRATIONS  xv 


FIG. 


97.  Two  transverse  sections  and  one  longitudinal  section  from  a 

case  of  subacute  combined  degeneration,  stained  by  the 
Marchi  method  .  .  .  .  .281 

98.  Disseminated  sclerosis.     Sections  of  pons  and  medulla         .      286 

99.  Disseminated  sclerosis.     Sections  of  cerebellar  cortex  and  of 

cord  (one  longitudinal  and  several  transverse  at  various 
levels  in  the  same  cord)  .  .  .  .      287 

100.  Syringomyelia  ......     294 

10 1.  Syringobulbia  ......      295 

102.  Myasthenia  gravis:  {a)  Drawing  of  transverse  section  of  an 

ocular  muscle  showing  a  "  lymphorrhage  ";  (b)  photo- 
graph of  transverse  section  of  a  skeletal  muscle  .      302 

103.  Diagram  of  Lange's  colloidal  gold  reaction    .  .  .     325 


PATHOLOGY  OF 
THE   NERVOUS   SYSTEM 

CHAPTER  I 
GENERAL  PATHOLOGY 

I.  Introduction. 

The  science  of  neuro-pathology  includes  the  study  not  only  of 
pathological  processes  limited  to  nervous  structures — the  nerve 
cell  and  its  processes — but  of  changes  in  other  structures  with 
which  the  nervous  system  is  intimately  associated  both  in  an 
anatomical  and  physiological  sense.  The  nerve  cells  and 
their  processes,  in  other  words  the  neurons,  may  exhibit 
states  of  health  which  are  at  variance  with  the  normal  for  a 
number  of  different  reasons.  In  the  first  place,  they  may 
never  reach  maturity,  or  may  lag  behind  the  rest  of  the  body 
in  the  process  of  development.  In  the  second  place,  they  may 
reach  maturity  with  an  inherent  lack  of  endurance  which 
prevents  them  from  completing  the  full  course  of  life.  Thirdly, 
they  may  suffer  from  over-activity  or  unnatural  idleness. 
Fourthly,  they  may  undergo  biochemical  or  nutritional  dis- 
turbance owing  to  changes  of  a  qualitative  or  quantitative 
character  in  the  fluids  on  which  they  are  dependent  for  their 
food.  Fifthly,  and  finally,  they  may  be  the  victims  of  patho- 
logical changes  in  neighbouring  tissues. 

Each  of  these  unhealthy  states  will  be  illustrated  in  some 
detail  in  the  pages  of  this  volume,  but  examples  may  be  cited 
here  in  order  that  the  principle  of  this  classification  may  display 
at  once  its  practical  bearing. 

1.  Agenesis  : — the  undeveloped  state  of  the  higher  cerebral 
centres  in  congenital  idiots. 

2.  Abiotrophy : — the  degeneration  in  early  adult  life  of 
certain  spinal  tracts  in  Friedreich's  ataxy. 


2  GENERAL  PATHOLOGY 

3.  (a)  Hyperactivity  : — the  cortical  cell  changes  found  after 
death  from  status  epilepticus. 

{b)  Disuse : — the  atrophic  changes  in  the  ventral  horn  cells 
of  the  spinal  cord  after  amputation  of  a  limb. 

4.  (a)  Intoxication  : — the  cell  changes  in  the  medulla  and 
spinal  cord  associated  with  diphtheritic  paralysis  or  with 
chronic  alcoholism. 

(b)  Ischaemia  : — the  cell  changes  resulting  from  disturbance 
of  the  blood  supply  to  any  part  of  the  nervous  system,  as  in 
cerebral  thrombosis. 

5.  {a)  Neuroglial  overgrowth  : — syringomyelia. 

{b)  Meningeal  disease  : — lepto-  or  pachy-meningitis. 

(c)  Compression  : — tumours  or  diseases  of  the  cranium  or 
vertebral  column. 

{d)   Vascular  disturbance  : — cerebral  or  spinal  haemorrhage. 

Our  knowledge  concerning  these  pathological  processes  has 
grown  hand-in-hand  with  the  advance  of  nervous  physiology 
during  the  last  seventy  years,  and  so  closely  related  and  inter- 
dependent are  neuro-pathology  and  neuro-physiology  that  it 
is  impossible  to  discuss  the  one  without  constant  reference  to 
the  other.  For  this  reason  it  is  desirable  to  refer  briefly  and 
immediately  to  some  of  the  well-established  physiological 
facts  which  have  intimate  pathological  bearings,  and  which 
have  added  so  much  to  our  acquaintance  with  the  histological 
anatomy  of  the  nervous  system. 

2.  The  Neuron. 

The  whole  of  present-day  neuro-histology  and  neuro-patho- 
logy has  been  built  up  on  the  basis  of  Waller's  experiments 
in  1850,  by  means  of  which  he  demonstrated  that  degenerative 
changes  take  place  throughout  the  whole  of  a  frog's  nerve  below 
the  point  at  which  it  has  been  divided.  This  experiment 
showed  not  only  that  degeneration  commences  at  once  and 
simultaneously  in  the  whole  of  that  part  of  the  nerve  fibre 
which  is  separated  from  the  nerve  cell,  but,  indirectly,  that  the 
cell  is  the  central  organ  for  the  formation  and  nutrition  of  all 
its  processes.  This  discovery  was  supplemented  later  by  Forel, 
who  observed  that  such  secondary  degeneration  does  not  extend 
through  the  cell-station  forming  the  link  between  two  physio- 
logically connected  fibres.      For  example,  the    degeneration 


THE  NEURON  3 

of  pyramidal  tract  fibres  cut  across  in  the  thoracic  region  of  the 
cord  can  be  traced  into  the  lumbo-sacral  enlargement,  but 
does  not  extend  through  the  ventral  horn  cells  of  that  region 
into  their  root  fibres  and  the  peripheral  nerves.  The  relation- 
ship of  the  cell  to  its  chief  process  was  still  further  illustrated 
by  the  experimental  work  of  von  Gudden,  who  first  noted  the 
cellular  changes  which  follow  injury  or  disease  of  its  axis 
cylinder  process. 

In  these  simple  facts  lie  substantially  the  foundation  of  the 
neuron  doctrine  which  holds  that  the  nervous  system  consists 
of  a  large  number  of  units,  each  composed  of  a  cell  and  its 
processes,  which  are  genetically  and  nutritionally  indepen- 
dent of  one  another,  although  closely  related  in  function 
and  variously  grouped  to  form  physiological  systems  and 
arcs. 

The  early  popularity  of  the  neuron  doctrine  twenty  years 
ago  was  followed  by  a  period  of  considerable  unrest  and 
doubt,  during  which  the  chief  bone  of  contention  was  the 
primary  origin  of  the  nerve  fibre  and  the  nature  of  its  regenera- 
tion after  injury.  Most  of  those  who  were  ready  to  give  the 
doctrine  an  indecently  hasty  burial  because  researches  seemed 
to  show  that  nerve  fibres  could  be  laid  down  by  sheath  cells  in 
segmental  fashion,  have  lived  to  see  its  prosperous  revival  on 
a  firmer  basis.  The  investigations  of  His,  Ramon-y-Cajal, 
Held  and  Ross  Harrison  have  all  contributed  to  this  end  by 
proving  conclusively  that  the  axis  cylinder  process  is  an  out- 
growth of  the  cell  protoplasm  and  is  not  dependent  on  sheath 
cells  for  its  origin  or  its  existence.  On  the  other  hand,  it  is 
generally  agreed  that  sheath  cells  play  a  considerable,  if  only 
accessory,  part  in  bringing  about  the  regeneration  of  peripheral 
nerve  fibres,  and  the  success  of  that  part  is  emphasised  by  the 
paucity  of  regenerative  power  in  the  fibres  of  the  central  nervous 
system  where  sheath  cells  do  not  exist.  Although  there  must 
remain  some  difference  of  opinion  with  regard  to  minor  points, 
there  is  at  the  present  time  general  agreement  in  favour  of  the 
view  that  the  neuron  is  a  distinct  unit,  especially  in  respect 
to  its  reaction  to  pathological  processes. 


4  GENERAL  PATHOLOGY 

(a)   The  Nerve  Cell. 

Although  the  ii^pregnation  methods  of  Golgi,  Ramon-y-Caj  al 
and  Bielschowsky  have  been  responsible  for  much  valuable 
information  concerning  the  anatomy  of  the  nervous  system 
and  the  external  form  of  the  nerve  cells  and  their  processes, 
our  knowledge  of  pathological  changes  occurring  within  the 
cells  owes  more  to  the  staining  method  invented  by  Nissl. 
The  Nissl  method  and  its  modifications  depend  for  their  value 
on  the  fact  that  certain  constituents  of  nerve  cells  are  readily 
stained  by  basic  aniline  dyes,  while  other  parts  remain  un- 
coloured.  Thus  the  coloured  or  chromatophile  structures 
include  the  nucleolus,  the  nuclear  membrane,  and  certain  bodies 
found  in  the  cell  protoplasm.  To  the  latter  have  been  applied 
a  variety  of  names,  such  as  Nissl  bodies,  chromatin  granules, 
tigroid  bodies,  etc. 

The  value  of  the  Nissl  method  lies  in  the  fact  that  we  are 
enabled  by  its  employment  to  detect,  in  some  cases  with  ease, 
any  abnormalities  with  regard  to  the  size  and  shape  of  the  cell 
body,  the  size,  shape  and  position  of  the  nucleus,  and  the 
disposition  and  appearance  of  the  chromatin  granules.  The 
methods  of  Ramon-y-Caj  al  and  Bielschowsky  reveal  the  neuro- 
fibrils of  the  cell  body  and  its  processes,  and  bring  into  prom- 
inence the  fibrillar  network  imbedded  in  the  homogeneous 
protoplasm.  While  some  authors  believe  that  the  distribution 
of  the  Nissl  bodies  is  determined  by  the  fibrillar  network,  and 
that  the  former  occupy  and  fill  the  meshes  of  the  latter,  others 
find  that  the  chromophile  substance  is  encrusted  upon  knots 
of  the  network  at  the  points  where  one  fibril  joins  another. 
In  this  way  the  Nissl  bodies  may  be  star-shaped,  rod-shaped, 
or  polyhedral  in  form.  Other  authorities  dispute  the  presence 
of  an  intracellular  network  at  all,  and  only  describe  neuro- 
fibrils passing  independently  through  the  cell  protoplasms  from 
one  process  into  another.  The  disadvantage  of  the  impregna- 
tion methods  for  pathological  investigation  is  brought  home  to 
us  by  these  conflicting  observations. 

On  the  other  hand,  the  Nissl  method  has  its  limitations. 
While  a  large  number  of  the  more  important  ganglion  cells 
of  the  nervous  system  are  eminently  suited  for  investigation 
by  this  method,  many  others  are  so  deficient  in  chromophile 


THE  NERVE  CELL 


a.  Normal  cells  from  hypoglossal  nucleus. 

b,  Normal  cell  from  ventral  horn  of  lumbar  enlargement  of  spinal  cord. 
Q,  Pigmentation  of  ventral  horn  cells  without  -pathological  significance. 


6  GENERAL  PATHOLOGY 

substance  and  display  such  variation  in  their  size  and  shape 
and  in  the  position  of  their  nuclei  that  very  special  knowledge 
and  experience  are  required  before  an  accurate  estimate  can 
be  formed  with  regard  to  the  presence  or  absence  of  abnormal 
features.  In  spite  of  this  drawback,  the  Nissl  method  has 
given  us  a  vast  amount  of  information,  and  is,  at  the  present 
time,  our  mainstay  in  the  study  of  nerve  cell  changes.  It  has 
been  employed,  in  both  experimental  and  human  pathology,  by 
many  skilled  observers,  and  results  have  been  obtained  not 
only  in  connection  with  the  chief  cells  of  the  brain  and  spinal 
cord,  but  also  in  observations  upon  the  peripheral  ganglia 
and  the  cells  of  the  sympathetic  system. 

Cell  changes  after  lesions  of  axis  cylinders. — It  has  been 
shown  that,  speaking  generally,  lesions  of  axis  cylinders  are 
followed  by  certain  changes  in  the  cells  of  their  origin.  This 
phenomenon  has  been  widely  studied  in  many  neurons  and  in 
many  animals;  the  changes  in  the  hypoglossal  nucleus  follow- 
ing division  of  the  hypoglossal  nerve  of  a  rabbit  may  be  taken 
as  an  example.  The  changes  may  be  divided  into  two  stages, 
the  reaction  stage  and  the  reparation  stage.  The  reaction 
stage  begins  within  forty-eight  hours  after  the  nerve  division 
and  reaches  its  zenith  at  the  end  of  fifteen  to  twenty  days. 
During  this  period  the  following  phenomena  may  be  observed 
in  the  majority  of  the  cells  of  the  nucleus,  (i)  Breaking 
down  of  the  chromatin  granules  into  a  fine  dust  which  still 
retains  the  colour  of  the  stain.  This  change  begins  in  the 
perinuclear  zone  and  spreads  towards  the  periphery  of  the  cell 
and  into  the  bases  of  the  cell  processes;  it  has  received  the 
name  of  chromatolysis  or  chromolysis.  Occasionally  the 
dust  loses  its  chromophilic  tendency,  the  whole  cell  becomes 
almost  colourless,  and  a  condition  of  "  achromatosis  "  is  estab- 
lished. (2)  The  cell  increases  in  volume,  loses  its  polygonal 
form,  and  becomes  rounded  and  swollen.  (3)  The  nucleus 
is  also  increased  in  size,  and  becomes  displaced  towards  the  cell 
margin  or  into  the  base  of  one  of  its  processes.  As  a  rule  the 
nucleus  retains  its  shape,  but  when  it  reaches  the  surface  of  the 
cell  it  may  become  more  oval,  with  its  long  axis  parallel  to  the 
cell  margin,  and  may  even  show  some  invagination  on  its 
inner  aspect.  The  nucleus  may  project  from  the  surface 
of  the  cell,  and  in  some  instances  is  completely   extruded. 


THE  NERVE  CELL  7 

This   event    is    followed  by   atrophy    and   disappearance   of 
the  cell. 

The  reparation  stage  is  of  longer  duration,  beginning  about 
the  twentieth  day  after  nerve  division  and  attaining  completion 
about  eighty  days  later,  by  which  time  the  cell  has  resumed 
its  normal  appearance.  During  this  period  the  chromatin 
granules  are  gradually  reformed  and  retake  their  place  in  the 


Fig.  2. 

Ventral  horn  cellsjshowing  changes  resulting  from  destruction  of  ventral  roots 
("  reaction  d,  distance  "). 

picture.  Meanwhile  the  cell  slowly  diminishes  in  size  and  the 
nucleus  regains  its  central  position.  Characteristic  of  the 
stage  of  repair  is  the  appearance  produced  by  a  somewhat 
enlarged  cell  filled  with  granules  which  are  bigger  and  more 
numerous  than  those  seen  in  the  normal  state.  This  is  the 
**  pyknomorphic  "  condition  of  Nissl. 

The  above  description  of  cellular  changes  cannot  be  univer- 
sally applied  to  all  cases  of  nerve  division.     Variations  are 


8  GENERAL  PATHOLOGY 

common  and  occur  in  two  directions.  In  the  first  place,  spinal 
nerves  may  be  divided  in  peripheral  parts  of  the  limbs,  and  a 
search  for  cell  changes  may  give  very  meagre  or  no  results. 
According  to  some  authors,  the  amount  of  reaction  varies 
directly  with  the  proximity  of  the  axis  cylinder  lesion  to  the 
cell  of  origin.  In  the  second  place,  the  character  of  the  injury 
to  the  axis  cylinder  appears  to  determine  the  amount  of  cell 


Fig.  3. 

Ventral  horn  cells  from  a  patient  dying  from  alcoholic  neuritis  showing  much 

vacuolation. 

change.  On  the  one  hand,  a  slight  lesion,  such  as  the  temporary 
application  of  a  ligature  to  a  nerve,  may  evoke  a  very  poor  and 
transient  reaction  which  rapidly  passes  into  the  stage  of  repara- 
tion, the  whole  process  lasting  a  comparatively  short  time. 
On  the  other  hand,  when  nerves  are  roughly  treated,  for 
instance  when  they  are  torn  apart,  the  cell  reaction  is  rapid  in 
onset,fulminant  in  character,  and  frequently  fails  to  be  followed 
by  reparation.     Thus  the  forcible  rupture  of  one  hypoglossal 


THE  NERVE  CELL  9 

nerve  in  a  rabbit  may  result  in  the  complete  disappearance 
of  all  cells  in  the  corresponding  nucleus  after  the  lapse  of 
thirty-five  days. 

As  far  as  human  pathology  is  concerned,  cell  reaction  to 
axonal  injuries  or  diseases  appears  to  be  fairly  constant,  and 
it  is  the  rule  to  find  cell  changes  and  a  more  or  less  complete 
disappearance  of  cells  in  the  corresponding  segments  of  the 
spinal  cord  after  limb  amputation.  According  to  some 
authors,  there  are  exceptions  even  to  this  rule. 

The  question  as  to  the  exact  nature  of  the  process  underlying 
the  cell  reaction  has  not  been  finally  settled,  but  it  appears 
probable  that  chromatolysis  depends  upon  an  increase  in  the 
fluid  content  of  the  cell. 

The  factors  on  which  the  process  of  repair  depends  have  also 
given  rise  to  a  conflict  of  views.  According  to  some  observers, 
the  reparation  stage  can  only  be  entered  upon  when  regenera- 
tion of  the  peripheral  portion  of  the  divided  axon  takes 
place.  According  to  others  it  is  equally  certain  that  complete 
reparation  of  the  cell  can  obtain,  under  some  circumstances, 
in  the  entire  absence  of  axonal  regeneration.  The  circum- 
stances determining  these  results,  however,  have  not  yet  been 
established. 

The  peripheral  sensory  neurons  have  been  investigated  in 
the  same  way,  and  with  results  which  present  many  similarities 
as  well  as  some  differences.  The  ganglion  cells  of  the  peri- 
pheral sensory  neurons  lie  outside  the  central  nervous  system 
and  are  bipolar  in  form ;  that  is  to  say,  they  possess  two  axonal 
prolongations,  central  and  peripheral,  cellulifugal  and  cellu- 
lipetal.  Division  of  the  peripheral  or  cellulipetal  axons  is 
generally  followed  by  a  stage  of  reaction  in  the  cells  of  origin, 
which  show  changes  resembling  those  described  in  connection 
with  the  motor  neurons.  Perinuclear  chromolysis,  enlarge- 
ment of  the  cell  body  and  lateral  displacement  of  the  nucleus, 
are  more  or  less  constantly  observed.  The  onset  of  those 
changes  is  detected  twenty-five  to  thirty  hours  after  the  nerve 
division  and  reaches  its  height  at  the  end  of  seven  days.  In 
the  majority  of  cases  the  reaction  is  followed  by  repair,  which, 
again,  is  of  shorter  duration  than  the  corresponding  stage  in 
motor  neurons.  In  other  instances  repair  does  not  take  place, 
and  a  larger  or  smaller  number  of  cells  undergo  atrophy  and 


10  GENERAL  PATHOLOGY 

destruction.    The  factors  determining  the  presence  or  absence 
of  the  reparatory  stage  are  still  unknown. 

Division  of  cellulipetal  fibres,  therefore,  produces  cell  changes 
which  only  differ  materially  from  those  of  peripheral  motor 
neuronic  cells  in  their  precocity.  When,  however,  central  or 
cellulifugal  axons  are  divided,  for  instance  by  section  of  the 
dorsal  spinal  roots,  cell  reaction  is  either  entirely  wanting 
or  occurs  in  doubtful  and  meagre  quantity  at  a  very  much 
later  period.  If  it  occurs  at  all,  it  takes  the  form  of  slight 
cellular  atrophy  associated  with  some  interstitial  proliferation 
in  ganglia  which  are  examined  many  months  after  the  operation. 
This  is  rather  in  accordance  with  the  general  experience  in 
human  pathology  that  degeneration  of  the  dorsal  roots  and 
sclerosis  of  the  dorsal  columns  is  often  unaccompanied  by 
any  changes  in  the  cells  of  the  dorsal  root  ganglia.  It  is 
worth  while  noting  in  this  connection  that  three  months  after 
division  of  the  dorsal  roots  some  myelin  degeneration  may  be 
found  in  the  terminal  parts  of  the  peripheral  fibres.  Similar 
but  less  marked  degeneration  may  be  found  in  the  dorsal 
roots  after  section  of  the  peripheral  sensory  axons. 

The  reaction  of  cells  which  lie  within  the  central  nervous 
system  and  whose  axons  are  distributed  within  the  brain  or 
spinal  cord  now  requires  our  attention.  There  appears  to  be 
little  or  no  doubt  that  division  of  these  axons  is  generally 
followed  by  changes  of  cellular  reaction  similar  to  those  de- 
scribed in  relation  to  peripheral  neurons,  and  it  is  equally 
certain  that  the  reaction  stage  is  never  followed  by  any  attempt 
at  repair.  It  is  usual  to  find  that  a  large  proportion  of  the  cells 
of  origin  proceed  to  atrophy  and  final  destruction.  This  rule 
holds  good  at  any  rate  for  the  pyramidal  tract  and  the  Betz 
cells  of  the  motor  cortex,  for  the  direct  cerebellar  tract  and  the 
cells  of  Clarke's  column,  and  for  Monakow's  bundle  and  the 
cells  of  the  red  nucleus.  According  to  some  authors,  the  prox- 
imity of  the  axonal  lesion  to  the  cells  of  origin  determines 
to  some  extent  the  intensity  of  cellular  reaction.  It  has  been 
found,  for  instance  in  human  pathology,  that  the  Betz  cells 
present  more  intense  and  more  rapid  signs  of  reaction  after 
lesions  of  the  internal  capsule  than  they  do  after  similar 
affections  of  the  pyramidal  path  in  the  medulla  or  spinal  cord. 
The  absence  of   cell  reparation  in  the  central  neurons  is  of 


THE  NERVE  CELL  ii 

interest  in  connection  with  the  well-known  failure  of  central 
axons  to  regenerate  after  a  breach  of  continuity,  and  may  be 
compared  to  the  more  general  facility  towards  cellular  repara- 
tion and  axonal  regeneration  which  is  possessed  by  peripheral 
neurons. 

In  the  sympathetic  system  there  is  considerable  difficulty 
in  determining  the  presence  of  chromolysis  and  nuclear  dis- 
placement in  the  ganglion  cells  on  account  of  their  scanty 
chromatophile  substance  and  variously  situated  nuclei  under 
normal  circumstances;  it  has,  however,  been  demonstrated 
that  cell  reaction  does  take  place  after  division  of  sympathetic 
cords.  Section  of  the  cervical  sympathetic  above  the  superior 
cervical  ganglion  leads  to  a  variable  amount  of  cell  enlarge- 
ment, chromolysis,  and  nuclear  displacement  in  the  latter,  and 
resection  of  the  hypogastric  plexus  has  been  shown  to  produce 
a  typical  axonal  reaction  in  the  intermedio-lateral  column  of 
cells  in  the  lumbo-sacral  region  of  the  cord. 

Further  details  of  the  axonal  reaction  of  cells  are  observed 
by  means  of  neuro-fibril  stains,  such  as  those  of  Ramon-y-Cajal 
and  Bielschowsky.  The  first  change  corresponds  in  time 
to  that  of  the  perinuclear  chromolysis,  and  consists  of  some 
disintegration  of  the  central  part  of  the  intracellular  fibrillar 
network.  Meanwhile,  the  more  peripheral  fibrils,  namely 
those  passing  through  the  cell  protoplasm  from  one  process  to 
another,  remain  intact.  The  central  part  of  the  neuro-fibril 
plexus  which  is  the  site  of  the  earliest  change  represents  the 
origin  of  the  axonal  process.  With  the  displacement  of  the 
nucleus  the  network  breaks  up  into  fragments  which  are  diffi- 
cult to  detect,  and,  if  the  reaction  is  intense,  the  peripheral 
fibrils  and  those  of  the  processes  also  undergo  granular  dis- 
integration. In  the  stage  of  repair  it  is  not  unusual  to  find 
cells  having  a  striated  appearance  due  to  the  absence  of  fibrillar 
network  and  the  preservation  of  the  long  fibrils  traversing  the 
cytoplasm.  Finally,  a  reconstruction  of  the  plexus  takes 
place,  and  the  normal  appearances  are  regained. 

In  conclusion,  emphasis  may  be  laid  on  the  fact  that  while 
cellular  reaction  to  axonal  lesions  is  very  general  in  human  and 
experimental  pathology,  there  appears  to  be  a  considerable 
variabiHty  in  the  amount  of  resistance  offered  to  this  process 
by  individual  cells.      It  is  the  rule  to  find  that  the  cells  of  any 


12  GENERAL  PATHOLOGY 

system,  although  all  exposed  to  the  same  insult  through  their 
axons,  do  not  all  respond  in  equal  fashion.  Some  do  not 
react  at  all,  others  react  but  recover,  while  the  remainder  pass 
through  the  stage  of  reaction  only  to  undergo  atrophy  and  final 
destruction. 

Cellular  reaction  to  physiological  and  pathological  influences. — 

While  the  axonal  reaction  of  nerve  cells  described  above 
may  be  regarded  as  a  more  or  less  specific  phenomenon,  the 
same  can  hardly  be  claimed  for  all  forms  of  cellular  changes 
associated  with  physiological  or  pathological  states.  It  is  not 
unusual  to  describe  axonal  reaction  as  a  secondary  cell  change, 
and  those  cell  changes  dependent  on  chemical  or  physical 
alterations  in  the  cellular  environment  as  primary. 

Rest. — Resting  cells  present  what  is  regarded  as  a  normal 
appearance,  but  there  is  some  reason  to  suppose  that  absolute 
cellular  rest,  that  is  to  say  a  condition  in  which  there  is  an 
unusually  large  reserve  of  energy,  is  characterised  by  the 
presence  of  numerous  and  large  compact  masses  of  Nissl 
chromatin  (Pyknomorphic  state). 

Activity. — Normal  activity  produces  a  diminution  in  the 
amount  of  chromophilic  substance  together  with  a  slight 
increase  of  the  volume  of  the  cell  and  its  nucleus  {parapykno- 
morphic  state). 

Exhaustion. — When  activity  goes  on  to  prolonged  exhaustion 
the  chromophilic  substance  becomes  broken  up  into  smaller 
particles,  and  both  the  cell  and  its  nucleus  may  tend  to  shrink. 
In  extreme .  degrees  of  exhaustion  the  cell  protoplasm  may 
show  some  vacuolisation,  and  it  is  often  surrounded  by  parasitic 
cells  of  neuroglial  or  vascular  origin  {neuronophagy) . 

Intoxication. — Cellular  reactions  occur  to  various  forms  of 
poisoning,  organic  and  inorganic,  exogenous  and  autogenous. 
There  is  nothing  characteristic  of  any  individual  poison;  in 
other  words,  the  cellular  appearances  give  no  certain  clue  as  to 
the  nature  of  the  toxic  agent  in  any  particular  case.  Chromo- 
lysis,  sometimes  achromatosis,  together  with  swelling  and 
vacuolisation  of  the  cell  body  and  displacement,  or  even  extru- 
sion of  the  nucleus,  are  features  common  to  many  forms  of 
intoxication  Chromolysis  may  begin  either  in  the  peripheral 
or  the  central  zone  of  the  cell  protoplasm.  An  attempt  to  show 
that  perinuclear  chromolysis  is  always  due  to  a  lesion  of  the 


THE  NERVE  CELL  13 

axis  cylinder,  while  peripheral  chromolysis  is  the  result  of 
primary  cell  affections,  has  not  been  substantiated.  While 
it  is  safe  to  say  that  axonal  reaction  is  always  associated  with 
perinuclear  chromolysis,  it  must  be  allowed  that  the  loss  of 
chromolytic  substance  in  the  primary  affections  may  begin 
either  centrally  or  peripherally.  According  to  some  authors, 
the  central  form  of  chromolysis  is  an  indication  that  the 
process  is  acute  and  virulent  in  type.  Speaking  generally, 
it  may  be  stated  that  the  effect  of  a  large  number  of  poisons  is 
to  produce  cell  changes  which  are  not  always  to  be  distinguished 
from  those  of  axonal  reaction. 

Circulatory  disorders. — Partial  interference  with  the  circula- 
tion may  bring  about  cell  changes  similar  in  type  to  those 
described  as  due  to  the  influence  of  various  poisons.  On  the 
other  hand,  sudden  and  complete  cutting  off  of  the  blood  supply 
from  any  part  of  the  central  nervous  system  leads  to  a  rapid 
cell  change  which  is  characterised  by  the  fact  that  the  cell  body 
is  reduced  in  size,  and  that  the  whole  of  the  protoplasm  and 
nucleus  is  stained  more  or  less  homogeneously  by  the  basic  dye. 
This  has  been  well  illustrated  by  the  results  of  experimental 
ligature  of  the  carotid  and  vertebral  arteries  or  of  the  abdominal 
aorta  in  animals,  and  by  the  results  of  local  thrombotic  lesions 
in  human  brains.  There  is  evidence  to  show  that  the  chromo- 
lysis, together  with  some  swelling  of  the  cell  and  displacement 
of  the  nucleus,  may  be  recovered  from  if  and  when  the  cir- 
culation is  re-established,  but  the  state  of  cell  shrinkage  asso- 
ciated with  uniform  deep  staining  indicates  a  biochemical 
change  in  the  protoplasm  from  which  recovery  is  impossible. 

Hyperpyrexia. — It  has  been  ascertained  experimentally  that 
the  exposure  of  nerve  cells  to  a  temperature  of  109°  F.  (43°  C.) 
rapidly  brings  about  a  change  which  is  characterised  by  the 
loss  of  differentiation  between  the  chromatic  and  achromatic 
constituents  of  the  cytoplasm.  The  cell  volume  is  somewhat 
increased,  and  the  whole  protoplasm,  as  well  as  the-  nucleus, 
becomes  more  or  less  uniformly  stained  by  the  aniline  dye. 
A  somewhat  vitreous  appearance  is  given  to  the  cell,  and  the 
contour  of  the  nucleus  tends  to  lose  its  definition.  In  some 
cases  there  is  evidence  to  show  that  this  chemical  change, 
amounting  to  a  coagulative  necrosis,  begins  in  the  processes 
and  peripheral  parts  of  the  cell  and  spreads  towards  the  centre. 


14  GENERAL  PATHOLOGY 

A  prolonged  exposure  to  a  temperature  between  107°  and  108°  F. 
has  a  similar  effect.  Identical  changes  have  been  found  in  the 
brain  and  spinal  cord  of  persons  who  have  displayed  a  high 
temperature  immediately  before  death  or  who  have  suffered  for 
some  time  from  considerable  fever.  The  common  association 
of  high  fever  in  human  beings  with  infective  processes  makes 
it  difficult  to  discriminate  between  the  results  of  pyrexia  and 
those  of  circulating  toxins,  but  there  is  little  doubt  that  the 
condition  of  coagulative  necrosis,  especially  when  all  the  nerve 
cells  are  more  or  less  uniformly  affected,  is  characteristic  of 
hyperpyrexia.  It  is  probable,  from  experimental  results, 
that  a  very  slight  degree  of  this  coagulative  change  in  the  cell 
periphery  is  not  incompatible  with  life  and  even  with  recovery 
of  cell  function.  It  is  interesting  to  note  that  the  cell  changes 
of  hyperpyrexia  have  been  found  also  in  animals  which  have 
died  as  the  result  of  exposure  to  powerful  sun-rays,  as  this  may 
throw  light  on  some  cases  of  sunstroke  or  insolation  in  human 
beings. 

Pigmentary  changes  in  the  nerve  cell. — Nerve  cells  may 
normally  contain  two  varieties  of  pigment — melanin  and  lipo- 
chromes.  (i)  Melanin  is  normally  present  in  some  of  the 
cells  of  the  basal  ganglia  and  brain-stem,  especially  in  certain 
nuclei,  such  as  the  substantia  nigra  and  the  substantia  ferru- 
ginea,  where  the  amount  of  melanin  pigment  in  the  nerve 
cells  gives  a  black  tinge  to  the  cut  surface  of  the  brain-stem. 
Apart  from  these  localities,  melanin  pigment  does  not  occur  in 
nerve  cells  even  in  pathological  conditions.  (2)  Lipochromes 
are  found  in  all  varieties  of  nerve  cells  in  adult  and  advanced 
life,  usually  as  a  small  mass  of  yellowish  pigment  lying  between 
the  nucleus  and  the  origin  of  the  axon.  The  pigment  stains 
fairly  intensely  with  Marchi's  method  and  with  Scharlach  R. 
In  many  degenerative  conditions  it  increases  in  amount,  and 
may  almost  entirely  fill  the  nerve  cell,  displacing  the  Nissl 
granules.  It  is  never  seen  in  a  part  of  the  nerve  cell  where 
Nissl  granules  are  also  present. 

(b)  The  Nerve  Fibre. 

When  a  peripheral  nerve  is  divided  certain  changes  take 
place  almost  immediately  both  in  the  proximal  and  distal 
portions. 


THE  NERVE  FIBRE  15 

Changes  in  the  proximal  portion. — The  myelin  sheath 
undergoes  fatty  degeneration  as  far  as  the  nearest  node  of 
Ranvier  or  a  segment  or  two  higher,  and  proUferation  of  the 
cells  of  the  neurolemma  sheath  does  not  extend  above  this 
portion  of  the  fibre.  Within  a  few  hours  of  the  nerve  division 
the  terminal  portions  of  the  axis  cylinders  are  seen  to  swell. 
The  interfibrillar  substance  increases  in  such  a  way  that  the 
fibrils  of  the  axon  become  separated  and,  as  it  were,  combed 
out  into  loose  strands.  The  latter  do  not  remain  tidy,  but  tend 
to  interlace  and  to  curl  up  into  complicated  and  plexiform 
structures,  to  which  various  descriptive  names  have  been 
applied,  such  as  button,  ring,  plaquette,  spiral,  etc.  From 
these  tangled  masses  soon  arise  a  number  of  young  and  delicate 
axis  cylinders  which  grow  forward  in  all  directions  to  penetrate 
the  cicatrix  uniting  the  cut  ends  of  the  nerve,  and  tend  generally 
to  follow  the  lines  of  least  resistance.  In  the  course  of  their 
forward  growth  many  divide,  and  some  develop  bulbous  ex- 
tremities. These  bulbs  are  cone-shaped  or  olive-shaped,  and 
may  be  compared  to  the  pseudopodial  cone  of  growth  which  is 
observed  in  the  developing  axon  of  the  embryo.  According  to 
other  authors,  the  bulb  is  the  entangled  end  of  an  axon  which 
has  met  with  a  temporary  obstacle  in  the  way  of  its  progress. 
It  should  be  pointed  out  that  not  all  the  newly  formed  fibres 
pass  straight  through  the  cicatricial  tissue.  Many  stray 
in  lateral  and  reverse  directions,  forming  a  plexus  of  much 
intricacy.  The  proportion  of  fibres  passing  through  the  cica- 
trix into  the  distal  end  of  the  nerve  probably  depends  largely 
upon  the  amount  of  connective  tissue  which  intervenes  and  the^ 
degree  of  resistance  which  it  offers  to  penetration.  This 
explains  the  more  rapid  regeneration  of  a  peripheral  nerve 
after  early  surgical  union  of  the  cut  ends,  as  compared  to  the 
slower  and  less  complete  process  which  obtains  when  the  cut 
ends  are  not  brought  into  contact  and  remain  separated  by 
scar  tissue.  Along  with  this  outgrowth  from  the  axon,  there 
is  an  outgrowth  of  the  sheath  cells  in  the  form  of  finger-like 
processes.  These  enclose  the  neuro-fibrils  in  all  their  ramifica- 
tions, and  some  eventually  unite  with  similar  processes  arising 
from  the  sheath  cells  of  the  peripheral  cut  end  of  the  nerve. 

Changes  in  the  distal  portion, — In  that  part  of  the  nerve  which 
is  separated  from  its  nutritional  centre  changes  take  place 


i6  GENERAL  PATHOLOGY 

rapidly  throughout  its  length,  affecting  the  axis  cylinders,  the 
medullary  sheath,  and  the  sheath  of  Schwann. 

The  axis  cylinder  swells  and  becomes  more  obviously 
fibrillated.  In  the  second  place,  it  becomes  varicose  or 
irregular  in  contour.  Vacuolation  and  granular  disintegra- 
tion (axolysis)  follow,  and  finally  the  debris  is  removed  by 
wandering  cells. 

The  myelin  exhibits  a  tendency  to  break  up  into  droplets 
which  stain  deeply  in  specimens  treated  by  the  Marchi  method. 
These  droplets  undergo  further  division  and  are  finally  absorbed 
or  removed  by  phagocytic  cells.     There  is  some  reason  to  sup- 


FlG.   4. 

A  single  nerve  fibrejunder going  Wallerian  degeneration' stained  by  the  Marchi 

method. 

pose  that  with  the  rupture  of  continuity  between  the  nerve 
cell  and  the  distal  portion  of  its  axon  digestive  ferments  are  set 
free  within  the  neurolemma  of  the  latter,  and  that  these  fer- 
ments excite  the  breaking  up  of  the  myelin  and  axis  cylinder. 

The  nuclei  of  the  sheath  of  Schwann  multiply  by  direct  and 
mitotic  division  with  such  rapidity  that  in  three  or  four  days' 
time  there  are  many  cells,  richly  provided  with  protoplasm, 
scattered  about  between  the  myelin  droplets.  They  penetrate 
the  disintegrated  interior  of  the  fibre  in  all  directions,  and  some 
of  them,  at  any  rate,  assume  the  role  of  scavengers.  Others  are 
represented  in  the  final  stage  of  degeneration  as  spindle-shaped 


THE  NERVE  FIBRE  17 

structures  occupying  the  site  from  which  the  axis  cyUnders 
have  disappeared,  and  so  maintaining  a  path  for  the  newly 
formed  axis  cyHnders  to  use  when  they  have  traversed  the 
intervening  scar  tissue.  There  is  also  an  outgrowth  from  the 
sheath  cells  nearest  the  cut  end  of  the  nerve  towards  the  proxi- 
mal portion,  and  if  it  does  not  reach  this,  it  forms  an  "  end 
bulb  "  similar  to  that  formed  on  the  proximal  cut  end  of  the 
nerve  in  every  respect,  except  that  it  contains  no  nerve  fibres. 

In  this  way  the  process  of  degeneration  passes  imperceptibly 
into  one  which  may  be  regarded  as  preparatory  to  regeneration. 
Owing  to  the  activity  of  the  sheath  cells  from  the  moment 
when  degeneration  begins,  dead  material  is  rapidly  removed 
and  all  necessary  measures  are  taken  for  promoting  the  antici- 
pated regeneration.  The  door,  as  it  were,  is  left  open  for  the 
reconstruction  of  a  nervous  pathway. 

The  next  step  in  the  process  of  regeneration  is  an  interaction 
between  the  axons  and  the  sheath  cells,  which  results  in  the 
formation  of  a  new  myelin  covering  for  the  former.  Finally, 
the  sheath  cells,  having  completed  the  numerous  and  important 
duties  allotted  to  them,  retire  again  into  comparative  obscurity 
by  reforming  a  normal  neurolemma  and  losing  the  greater 
part  of  their  protoplasmic  structure.  The  reconstruction  of 
the  complete  nerve  fibre  takes  place  earlier  at  the  central  end 
of  the  distal  portion  than  it  does  in  the  periphery,  and  the  whole 
process  of  degeneration  and  regeneration  is  one  which  occupies 
some  months  even  under  the  most  favourable  circumstances. 

If,  instead  of  a  simple  division,  a  length  of  nerve  is  resected, 
regeneration  is  either  much  retarded  or  rendered  impossible. 
Even  in  these  conditions  some  regeneration  may  be  promoted 
by  the  artificial  interposition  of  a  graft  between  the  separated 
ends  of  the  nerve.  The  graft  directs  the  growth  of  the  re- 
generating fibres  towards  the  peripheral  end,  and,  as  far  as  is 
known,  has  no  vital  influence  on  regeneration. 

So  far  we  have  described  the  phenomena  attending  a  complete 
rupture  or  resection  of  a  nerve.  But  other  pathological 
processes  are  common  which  tend  to  injure  or  compress  nerve 
fibres  without  severing  their  continuity.  In  proportion  to 
the  severity  of  the  lesion  changes  are  produced  in  the  sheaths 
and  axis  cylinders  of  the  fibres,  but  it  does  not  follow  that  loss 
of  conductivity  from  the  clinical  point  of  view  is  necessarily 


i8  GENERAL  PATHOLOGY 

associated  with  destruction  of  the  axis  cyUnders.  On  the 
contrary,  there  may  be  local  changes  in  the  myelin  and  neuro- 
lemma sheaths  and  even  some  structural  alteration  of  the  axis 
cylinders,  with  loss  of  function  in  the  latter,  without  degenera- 
tion of  the  fibre  beyond  the  site  of  the  lesion.  In  this  way 
cases  of  rapid  return  of  function,  following  modification  of  the 
pathological  process  producing  paralysis  or  anaesthesia  in  the 
distribution  of  a  nerve,  are  easily  explained.  Some  cases  of 
Bell's  palsy,  for  instance,  recover  rapidly  in  a  few  days  even 
though  the  initial  lesion  has  been  severe  enough  to  cause 
complete  facial  paralysis.  In  other  instances,  nine  to  twelve 
months  elapse  before  the  process  of  regeneration  permits  of  the 
return  of  function. 

3.  The  Neuroglia. 

The  neuroglia  has  a  common  origin  with  the  nerve  cells  and 
their  processes  from  the  cells  of  the  neural  groove.  It  appears, 
however,  normally  to  act  purely  as  a  supporting  structure. 
In  the  early  months  of  extra-uterine  existence  it  may  serve 
to  some  extent  as  an  insulator  for  nerve  fibres  in  the  unmyelin- 
ated tracts  of  the  cord.  The  ependyma  lining  the  ventricles, 
the  iter  of  Sylvius  and  the  central  canal  of  the  cord,  as  well  as 
the  cells  covering  the  choroid  plexus,  have  a  similar  origin  to  the 
neuroglia,  and  may  be  considered  as  specialised  glial  structures. 
Of  their  changes  in  pathological  conditions  we  know  very  little, 
but  they  resemble  the  neuroglia  in  a  tendency  to  degenerate 
and  disappear  in  various  morbid  conditions.  The  central 
canal  of  the  cord  is  not  usually  preserved  in  adult  life,  but  an 
irregular  clump  of  ependymal  cells  can  always  be  seen  lying 
in  the  middle  of  the  grey  commissure,  and  in  destructive  lesions 
of  the  cord  these  cells  may  show  evidence  of  proliferation. 

The  neuroglia  cells  as  seen  in  the  brain  of  a  healthy  young 
adult  are  of  three  types. 

(i)  The  commonest  form  which  is  found  everywhere  in  the 
brain  and  cord  is  composed  of  a  small  cell  body  and  long,  un- 
branched,  filamentous  processes.  It  has  a  small,  round,  eccen- 
trically placed  nucleus  which  almost  fills  the  cell  body,  and  in 
which  the  chromatin  is  disposed  chiefly  as  fine  dots  on  the  inner 
surface  of  the  nuclear  membrane. 

(2)  Another  form,  seen  in  the  grey  matter,  has  relatively 


THE  NEUROGLIA  19 

short  branching  processes,  one  of  which  may  be  attached  to  the 
wall  of  a  blood  vessel. 

(3)  The  third  type,  seen  typically  in  the  cerebellar  cortex, 
has  three  or  four  thick  processes  which  branch  into  leashes 
of  fine  parallel  fibres  covered  with  small  swellings  or  spines. 
These  run  direct  to  the  surface  of  the  cerebellum  and  attach 
themselves  to  the  pia  mater.  This  type  of  cell  is  sometimes 
known  as  a  "  Deiter's  cell." 

When  stained  by  Weigert's  neuroglia  stain  it  is  seen  that 
glial  fibres  pass  through  the  cell  body  and  do  not  blend  with  it, 
but  in  immature  cells  the  peculiar  staining  of  the  fibres  becomes 
lost,  and  the  fibres  broaden  out  as  they  approach  the  cell  body. 
Glial  fibres  run  for  considerable  distances  in  all  directions, 
mainly  parallel  to  the  nerve  tracts,  but  may  pass  across  the 
fibres  of  several  different  tracts;  this  may  explain  the  fact  to 
which  Eurich  has  drawn  attention  that  a  neuroglial  sclerosis 
secondary  to  degeneration  of  one  tract  may  produce  glial 
thickening  among  the  fibres  of  the  neighbouring  tracts. 

The  walls  of  the  ventricles,  the  iter  of  Sylvius,  and  the 
central  canal  of  the  cord,  are  supported  by  an  increase  in  the 
glial  tissue,  and  on  the  surface  of  the  brain  and  cord,  in  the 
subpial  layer,  there  is  also  a  condensation  of  glial  fibres.  Here, 
and  around  the  walls  of  the  blood  vessels,  the  glial  fibres  form 
loose  connections  with  the  connective-tissue  fibres  by  means 
of  small  thickenings  or  foot-plates  attached  to  the  outer 
surface  of  the  connective  tissue. 

When  degeneration  of  nerve  elements  takes  place  from  any 
cause  the  neuroglia  reacts,  and  by  multiplication  of  cells  and 
fibres  replaces  the  disintegrated  parenchymatous  tissue.  It 
also  takes  on  a  phagocytic  or  "  scavenging  "  function,  and 
helps  in  the  removal  of  debris.  Glial  cells  also  join  with  cells 
of  vascular  origin  in  the  process  of  **  neuronophagy."  This 
term  does  not  mean  that  glial  and  other  cells  directly  attack 
degenerated  nerve  cells,  but  rather  that  they  absorb  from  them 
and  the  fluids  surrounding  them  the  products  of  degeneration. 
This  process  has  also  been  termed  "  necrophagy,"  but  as  cells 
are  often  seen  surrounding  nerve  cells  which  are  obviously 
not  dead,  and  which  probably  are  able  to  recover,  it  is  no  more 
exact  than  the  better-known  term.  The  cells  of  the  sheath 
of  Schwann  have  a  similar  origin  to  the  neuroglia  cells,  and  are 


20  GENERAL  PATHOLOGY 

analogous  to  them,  and  it  has  been  seen  that  cells  derived  from 
them  may  exercise  similar  phagocytic  powers. 

NeurogHal  overgrowth  may  take  place  without  any  obvious 
primary  nerve  degeneration,  as  in  syringomyelia  and  in 
tuberous  hypertrophic  sclerosis.  These  conditions  form  a 
connecting-link  between  reactionary  glial  proliferation  and 
tumour  formation.  In  gliomata  are  found  all  the  forms  of 
glia  cells  which  are  usually  seen  in  neuroglial  reaction,  those 
which  represent  earlier  and  less  specialised  stages  being  most 
numerous.  Abnormal  forms  with  ring-  or  horseshoe-shaped 
nuclei  may  also  appear. 

The  various  forms  of  reactionary  glia  cell  have  been  investi- 
gated by  special  staining  methods  by  Alzheimer,  who  attri- 
buted different  functions  to  the  different  forms.  Of  these 
we  may  note  the  following : 

(i)  Miniature  glia  cells,  which  occur  both  in  the  grey  and 
white  matter,  are  small  cells  resembling  lymphocytes,  with 
comparatively  little  cytoplasm.  Their  nuclei,  which  are 
usually  single,  are  similar  to  those  of  the  larger  form,  the  chro- 
matin being  scanty  and  in  the  form  of  granules,  chiefly  around 
the  periphery  of  the  cell.  These  cells  may  become  enlarged 
and  loaded  with  degeneration  products.  They  probably  arise 
directly  from  the  pre-existing  glial  cells  by  a  process  of  enlarge- 
ment and  division  of  their  cell  bodies.  They  may  go  on  to  form 
either  type  (2)  or  (3) . 

(2)  Amoeboid  glia  cells  :  Large  variety. — These  occur  in  the 
white  matter  of  the  brain  and  cord  at  a  later  stage  than  type  (i) 
in  all  forms  of  degeneration.  They  are  large  balloon-like 
cells  of  the  average  size  of  a  ganglion  nerve  cell,  with  one  or 
more  nuclei,  which  are  usually  eccentrically  placed.  Their 
cytoplasm  is  clear  or  finely  granular,  and  may  contain  various 
particles  which  stain  differently  with  aniline  dyes,  some  colour- 
ing with  acid  fuchsin,  some  with  methylene  blue,  etc.  Lipoid 
substances  may  also  be  present  in  the  cytoplasm.  Their 
inclusions  seem  to  arise  from  degeneration  products  of  myelin 
and  nerve  cells,  and  to  be  taken  up  in  solution  by  the  glial 
cells  and  by  them  transformed  into  simpler  products  which  can 
be  ingested  by  the  mesoblastic  cells.  These  amoeboid  glia 
cells  seem  to  have  considerable  migratory  powers,  and  they  are 
frequently  found,  loaded  with  granular  inclusions  and,  it  may 


THE  NEUROGLIA  21 

be,  themselves  undergoing  degeneration,  in  close  relation  to  the 
vessels.  From  this  situation  their  work  is  continued  by  the 
mesoblastic  cells,  which  appear  to  have  more  powers  of  fat 
metabolism  than  the  glial  elements  (fig.  30). 

(3)  Fibre-forming  glia  cells. — These  cells  are  similar  to  the 
large  amoeboid  glia  cells,  but  send  out  shoots  of  cytoplasm  in 
various  directions.  These  processes  are  considerably  thicker 
and  much  more  irregular  than  glial  fibres,  some  being  short  like 
pseudopodia,  others  longer  and  approximating  more  closely 
to  the  processes  of  spider  cells.     This  type  of  cell  frequently 


:^ 


t^^<t^ 


Fig.  5. 
Enlarged  neuroglia  cells  in  the  lateral  columns  of  the  cord  underlying  a  tumour. 

contains  granules,  and  is  evidently  closely  related  to  the  large 
amoeboid  type. 

(4)  Spider  cells  have  longer  and  finer  processes  than  the 
preceding  form.  Their  protoplasm  is  scanty  and  collected 
evenly  round  the  nucleus.  They  do  not  contain  granules. 
They  appear  to  arise  from  the  fibre-forming  type,  and  to 
represent  a  later  stage  in  the  development  of  the  mature 
glia  cell. 

To  sum  up  the  neuroglial  reaction,  it  may  be  said  that  in  any 
process  of  degeneration  of  axis  cylinders  or  ganglion  cells  the 


22  GENERAL  PATHOLOGY 

neuroglial  cells  proliferate,  giving  rise  to  cells  with  larger 
nuclei,  more  cytoplasm,  and  less  definite  fibres.  Some  of  these 
have  migratory  powers,  and  are  phagocytic  to  some  degree,  but 
seem  for  the  most  part  to  absorb  degeneration  products  in 
soluble  form,  and  from  them  to  elaborate  granules  of  various 
kinds,  which  they  store  in  their  cytoplasm  for  a  time  and  release 
either  by  a  new  process  of  solution  or,  more  probably,  by 
themselves  becoming  disintegrated.  Either  the  cells  or  the 
released   granules   are   ingested   by   mesoblastic   phagocytes. 


I 


.^1 
1      . 


* 


V.     ^;• 


k  ■   ■■ 


Neuroglial  thickening" in  an  old  focus  of  softening  in  the  cerebellum.  (From 
preparation  stained  by  Prof.  Carl  Weigert,  through  the  kindness  of  Dr.  Gordon 
Holmes.) 

Other  neuroglia  cells  pass  from  the  amoeboid  stage  through  the 
fibre-forming  to  the  spider-cell  stage  and  take  part  in  the  over- 
growth of  glial  tissue  which  replaces  the  degenerated  neuron 
substance.  We  may  infer  that  this  is  the  goal  to  which  all 
neuroglia  cells  tend,'when  the  process  is  not  interrupted  by  the 
exercise  of  their  phagocytic  powers.  At  the  stage  of  the  fibre- 
forming  glial  cell  the  cell  body  is  relatively  abundant  and  the 
processes  shorter  and  thicker  than  in  the  mature  form,  to  which 
the  cell  passes  through  the  spider-cell  stage,  its  body  becoming 
smaller  and  its  processes  longer  and  more  filamentous.     When 


THE  NEUROGLIA  23 

the  sclerosis  is  complete  very  little  is  seen  beyond  a  dense  mass 
of  neuroglial  fibres  with  a  few  small  rounded  nuclei. 

A  study  of  the  glial  reaction  in  degenerated  tracts  at  varying 
periods  after  injuries  of  the  spinal  cord  gives  some  idea  of  the 
time  taken  in  the  evolution  of  the  different  types  of  glial  cell. 
Within  the  first  month  only  types  (i)  and  (2)  are  represented, 
whereas  by  the  end  of  the  third  month  type  (3)  has  also  begun 
to  appear,  but  no  new  formation  of  glial  fibres  has  taken  place. 
By  the  sixth  month  spider  cells  have  become  numerous,  and 

PS^/\*-       •.  #•  m  •    '-  ■•'■•1 


Fig.  7. 
Section  from  spinal  cord  showing  many  corpora  amylacea. 

there  is  considerable  increase  of  glial  cells  and  sclerosis.  The 
spider-cell  type  persists  until  the  last  traces  of  degenerated 
myelin  have  disappeared,  and  may  still  be  fairly  numerous 
at  the  end  of  a  year  from  the  date  of  injury. 

The  stimulus  which  evokes  neuroglial  reaction  seems  usually 
to  be  purely  chemical,  and  arises  from  the  presence  of  degenera- 
tion products  of  nervous  tissue.  The  amount  of  the  reaction 
seems  to  be  proportional  to  the  amount  of  neuron  or  myelin 
degeneration.  And  it  is  owing  to  the  increase  of  glial  fibres 
resulting  from  this  process  that  many  forms  of  degeneration  of 


24  GENERAL  PATHOLOGY 

the  brain  or  spinal  cord  have  been  called  "  sclerosis,"  although 
their  initial  pathological  process  is  destructive  rather  than 
hyperplastic. 

Corpora  amylacea. — These  are  spherical  bodies,  from  lo  to 
40  /i  in  diameter,  and  often  showing  a  slight  degree  of 
concentric  lamination,  which  are  normally  found  in  the  cords 
of  elderly  subjects,  being  most  common  round  the  periphery 
of  the  cord,  but  present  in  both  grey  and  white  matter.  They 
stain  diffusely  blue  with  haematoxylin  stains,  especially 
Weigert's  iron  haematoxylin.  Owing  to  their  hard  consistency, 
and  possibly  to  the  presence  of  lime  salts  in  them,  they  may 
make  cords  which  contain  them  in  large  numbers  difficult  to 
cut  by  the  paraffin  method.  They  appear  to  be  derived  from 
neuroglia,  as  they  may  be  found  in  gliomata,  but  their  mode  of 
origin  is  unknown.     They  have  no  pathological  significance. 

4.  Paths  of  Infection  in  the  Central  Nervous  System. 

The  central  nervous  system  may  be  invaded  by  organisms 
or  their  toxins  either  by  the  blood  stream  or  by  the  lymph 
channels  of  the  cranial  and  spinal  nerves. 

{a)  Infection  by  the  hlood  stream  occurs  when  organisms 
are  carried  to  the  brain  and  cord  either  free,  as  in  septicaemia, 
or  contained  in  small  masses  of  pus,  as  in  bronchiectasis,  or  in 
septic  clot,  as  in  ulcerative  endocarditis  and  aortitis.  More 
rarely  the  spinal  cord  is  infected  in  this  way.  Any  of  these 
causes  may  result  in  the  formation  of  abscesses  in  the  brain  or 
cord,  which  are  usually  single  in  cases  of  bronchiectasis  or  endo- 
carditis and  multiple  in  cases  of  septicaemia. 

Or  the  nervous  system  may  be  attacked  by  organic  or  inor- 
ganic poisons  which  circulate  in  the  blood.  Some  well-known 
poisons,  such  as  alcohol,  arsenic,  and  lead,  may  affect  both  the 
central  and  peripheral  nervous  systems.  Others,  less  well 
understood,  spare  the  peripheral  nerves  and  cause  lesions  in  the 
brain  and  cord.  Among  these  must  be  reckoned  those  toxic 
.conditions  of  the  blood  which  give  rise  to  the  histological  picture 
known  as  "  combined  degeneration  of  the  spinal  cord."  Of 
the  poisons  which  cause  this  we  are  in  almost  complete 
ignorance.  It  is  known  that  this  form  of  degeneration  occurs 
in  pernicious  and  other  anaemias,  including  those  of  Addison's 
disease  and  the  cancerous  cachexia,  but  it  may  occur  without 


INFECTION  BY  BLOOD  STREAM  25 

any  anaemia,  and  may  get  worse  as  the  anaemia  improves. 
It  is  generally  considered  as  being  caused  by  toxins  arising  in 
the  gastro-intestinal  tract,  a  theory  which  has  received  remark- 
able support  from  the  work  of  Orr  and  Rows.  These  observers, 
in  the  course  of  a  long  research  on  the  paths  of  infection  of  the 
central  nervous  system,  put  one  or  more  celloidin  capsules 
containing  living  cultures  of  Staphylococcus  aureus  into  the 
abdominal  cavity  of  rabbits,  and  after  a  lapse  of  three  to  six 
weeks  found  evidence  of  cord  degeneration,  unassociated  with 
any  sign  of  inflammation  either  in  the  pia  arachnoid  or  in  the 
vessels  of  the  cord.  There  was  a  considerable  degree  of  glial 
proliferation,  especially  around  the  vessels,  and  some  early 
chromatolysis  of  the  nerve  cells.  These  changes,  however, 
were  slight  compared  to  the  degeneration  of  fibres  as  shown 
by  the  Marchi  method.  This  affected  especially  the  periphery 
of  the  cord,  which  everywhere  showed  numerous  droplets  of 
degenerated  myelin.  In  the  dorsal  columns  the  degenera- 
tion was  irregular,  affecting  the  dorso-median  fibres  at  some 
levels,  but  everywhere  sparing  the  root-entry  zone.  Many 
cells  laden  with  the  products  of  myelin  degeneration  were  seen 
in  relation  to  the  degenerated  areas  of  the  cord,  and  also  within 
the  adventitial  space  of  the  dorso-median  vein.  The  vessels 
of  the  cord  were  dilated,  and  contained  a  very  few  lymphocytes 
in  their  adventitial  spaces.  In  other  experiments,  where  the 
effects  of  the  toxin  were  more  severe,  some  vessels  were  throm- 
bosed and  all  showed  hyaline  changes  in  their  walls.  Orr  and 
Rows  take  the  view  that  the  cord  degeneration  in  these  experi- 
ments was  not  due  to  the  direct  effects  of  the  toxin  on  the  nerve 
fibres,  but  to  an  alteration  of  the  circulation  within  the  cord, 
resulting  from  the  action  of  the  toxin  on  the  sympathetic 
ganglia  in  the  abdomen. 

Degeneration  of  a  similar  type  is  found  in  pellagra  and 
lathyrism.  Whether  the  poisons  in  these  diseases  are  formed 
outside  the  body  or  arise  in  the  body  as  a  result  of  faulty  meta- 
bolism is  at  present  unsettled.  In  ergotism,  in  which  the  poison 
is  supposed  to  be  ingested  as  such,  a  similar  degeneration  of  the 
spinal  cord  may  occur.  It  is  to  be  noted,  however,  that  in 
these  conditions  the  brunt  of  the  degeneration  tends  to  fall  on 
the  dorsal  columns  rather  more  constantly  than  in  "  sub- 
acute combined  degeneration."     It  is  therefore  possible  that 


26  GENERAL  PATHOLOGY 

in  them  the  poison  attacks  the  cord  both  by  the  medium  of 
the  blood  stream  and  the  lymph  channels,  and  that  they  form  a 
connecting-link  between  haematogenous  and  lymphogenous 
infections  of  the  cord. 

(b)  Infection  of  the  nervous  system  by  way  of  the  lymphatics 
of  the  cranial  and  spinal  nerves  has  long  been  known  to  occur 
in  diphtheria  and  tetanus,  and  it  now  seems  to  be  proved  that 
these  toxins  cannot  reach  the  central  nervous  system  by  any 
other  route.  There  appears  to  be  a  free  lymphatic  flow  up  and 
down  the  cord  and  into  the  medulla  and  brain  stem,  and  in 
certain  cases  of  tetanus  it  is  possible  to  follow  the  march  of 
the  disease  in  an  upward  direction  from  the  lower  limbs  to  the 
parts  supplied  by  the  bulbar  and  pontine  nuclei.  We  know  of 
no  chemical  or  alkaloidal  poisons  which  reach  the  nervous 
system  in  this  way,  but  it  appears  to  be  a  common  route  of 
invasion  by  organisms  and  their  toxins.  Thus  myelitis  in  the 
upper  dorsal  or  lower  cervical  region  may  be  traced  to  a  focus  of 
chronic  suppuration  in  relation  to  the  pleura,  or  in  the  lower 
thoracic  and  lumbar  region  to  bed-sores  or  an  infected  psoas 
abscess.  As  will  be  seen  later  in  discussing  tetanus  (p.  191),  the 
dorsal  root  ganglia  seem  to  form  a  filter  for  toxins  and  a 
first  line  of  defence  against  micro-organisms,  their  invasion 
being  often  signalised  by  attacks  of  root  pain  or  herpes.  It  is 
probable  also  that  trigeminal  neuralgia  is  caused  by  the  in- 
vasion of  the  Gasserian  ganglion  by  organisms  or  their  toxins 
ascending  the  trigeminal  nerve  from  the  teeth,  and  some 
cases  of  recurring  herpes  limited  to  one  side  of  the  face  probably 
have  a  similar  aetiology. 

The  work  of  Orr  and  Rows  dealt  largely  with  this  type  of 
invasion.  They  placed  celloidin  capsules  containing  living 
broth  cultures  of  micro-organisms  in  contact  with  the  sciatic 
nerves,  or  under  the  skin  of  the  cheek  of  rabbits,  and  left  them 
in  position  for  periods  of  fourteen  days  to  six  weeks.  In  the 
latter  experiments,  in  addition  to  inflammatory  changes  in  the 
neighbourhood  of  the  capsule  and  in  the  lymphatics  of  the  neigh- 
bouring cranial  nerves,  they  found  degeneration  of  the  roots 
of  all  the  oculo-motor  nerves  and  both  motor  and  sensory 
branches  of  the  trigeminal.  This  degeneration  was  only  present 
in  the  part  of  the  nerve  which  lay  within  the  central  nervous 
system,  i.e.  where  the  nerve  fibres  were  surrounded  by  glia. 


INFECTION  BY  LYMPHATICS  27 

No  degeneration  of  fibres  could  be  seen  in  the  portions  of  the 
nerves  outside  the  brain-stem.  This  might  be  attributed  either 
**  to  the  vital  action  of  the  neurolemma  sheath,"  or  to  the  fact 
that  the  lymph  vessels  in  the  nerves  lie  peripherally  in  the 
sheath  of  the  nerve  and  not  among  its  fibres.  In  the  experi- 
ments where  the  capsule  was  placed  in  contact  with  the  sciatic 
nerves  a  similar  degeneration  of  fibres  was  found  in  the  dorsal 
root  zone  and  in  the  dorsal  columns  of  the  cord,  as  well  as 
in  the  ventral  roots  within  the  cord.  The  collaterals  leaving 
the  dorsal  columns  were  also  affected  to  some  extent.  Here 
again  the  degeneration  only  affected  the  nerve  fibres  after 
they  had  lost  their  neurolemma  sheath. 

(c)  Inflammatory  cellular  reaction  in  the  central  nervous 
system. — ^Although  the  processes  of  inflammation  in  the  central 
nervous  system  are  in  nature  identical  with  those  occurring 
elsewhere  in  the  body,  there  are  two  structural  differences 
which  modify  these  processes  and  alter  the  histological  picture. 
These  are  (i)  the  special  formation  of  the  walls  of  the  blood 
vessels,  and  (2)  the  glia. 

(i)  Both  arteries  and  veins  in  the  central  nervous  system  are 
surrounded  by  a  connective-tissue  sheath  derived  from  the  pia 
mater  which  invests  vessels  of  all  sizes  except  the  finest  capil- 
laries. Between  this  and  the  walls  of  the  vessel  are  lymphatic 
channels  which  are  in  fairly  free  communication  with  the  sub- 
arachnoid space.  These  adventitial  lymphatics  act  as  a  collect- 
ing station  for  phagocytic  and  reactionary  cells  of  various 
kinds  on  their  way  back  to  the  blood  stream  from  the  nervous 
tissues.  For  this  reason  it  is  common,  in  all  forms  of  inflam- 
mation of  the  brain  or  cord,  to  find  these  spaces,  especially 
those  round  the  veins,  packed  with  cells.  It  is  probable,  as 
will  be  seen  later,  that  certain  phases  of  myelin  destruction  and 
alteration  take  place  chiefly  in  this  situation. 

The  view  held  by  Nissl  that  cells  of  blood  origin  do  not  tend 
to  pass  into  the  nervous  tissues  except  when  these  are  acutely 
inflamed  must  now  be  modified  to  some  extent.  It  is  true  that 
in  many  degenerative  diseases  cells  of  a  blood  or  connective 
tissue  origin  are  not  found  except  in  relation  to  the  walls  of  the 
vessels,  but  whenever  the  nervous  tissues  are  actually  inflamed, 
either  acutely  or  in  a  more  chronic  manner,  cells  derived  from 
vascular  tissues  can  be  found  at  a  distance  from  any  blood 


28  GENERAL  PATHOLOGY 

channel,  and  in  the  more  acute  inflammations  of  the  brain  it  is 
common  to  find  cells  lying  in  chains  just  outside  the  capillary 
walls,  as  though  they  had  recently  escaped  from  the  blood 
stream.  Certain  of  these  cells  have  less  active  migratory 
powers  than  others,  and  some,  such  as  plasma  cells  and  endo- 
thelial cells,  are  most  frequently  encountered  near  the  vessels ; 
but  they  may  at  times  pass  farther  into  the  nervous  tissues, 
and  may  even  be  found  close  to  nerve  cells.  Apart  from  the 
restrictions  imposed  by  the  adventitial  lymph  spaces,  the 
reaction  on  the  part  of  cells  of  vascular  and  connective  tissue 
origin  towards  various  types  of  micro-organism  differs  in  no 
respect  from  that  seen  elsewhere  in  the  body,  with  this  excep- 
tion, that  as  fibrous  tissue  is  normally  scanty  in  the  central 
nervous  system,  the  proliferation  of  cells  of  fibrous  tissue  origin 
is  slower  and  less  profuse.  Thus  an  abscess  in  the  brain  is  apt 
to  spread  before  it  is  firmly  surrounded  by  fibrous  tissue,  and 
it  is  not  uncommon  to  find  a  chain  of  abscesses,  suggesting  that 
some  part  of  the  wall  of  each  has  been  too  poorly  formed  to 
limit  the  infective  process. 

(2)  The  glia  modifies  the  processes  of  inflammation  in  several 
ways.  In  the  first  place,  its  meshes  are  so  loose  that  once 
micro-organisms  have  found  their  way  into  the  nervous  tissues 
they  commonly  spread  in  a  diffuse  and  rapid  manner,  producing 
a  myelitis  or  encephalitis  which  has  little  tendency  to  become 
circumscribed.  Again,  the  powers  of  defence  which  the  glia 
can  exert  against  microbial  invasion  are  very  limited  and  in- 
adequate. It  is  true  that  glial  cells  respond  to  the  presence  of 
weak  toxins  by  proliferating  and  enlarging,  but  this  is  a  slow 
process  as  compared  with  that  of  endothelial  and  fibrous  tissues. 
They  are  also  much  more  vulnerable  than  the  latter,  and  are 
poisoned  and  killed  by  toxins  which  leave  fibrous  tissue  cells 
undamaged.  On  the  other  hand,  they  have  very  special  powers 
of  reaction  to  the  degeneration  of  nerve  cells  and  their  processes, 
especially  degeneration  of  the  myelin  sheath.  When  this 
occurs  they  respond  by  multiplication  and  the  formation  of  the 
large  and  small  amoeboid  forms  already  noted.  These  appear 
to  absorb  fatty  substances,  becoming  swollen  and  granular, 
and  forming  one  type  of  the  so-called  compound  granular 
corpuscle  (kornchenzell,  gitterzell,  corps  granuleux).  These 
appear  as  large  globoid  cells  with  a  fairly  small  eccentrically 


INFLAMMATORY  REACTION  29 

placed  nucleus,  and  in  paraffin  or  celloidin  sections  a  reticulated 
cytoplasm.  In  sections  stained  for  fat  by  osmic  acid  or  Schar- 
lach  R.  many  of  these  granules  stain  strongly.  These  cells 
appear  in  every  degenerative  disease  of  the  nervous  system, 
and  when  the  destruction  of  the  myelin  sheaths  is  extensive, 
as  in  tumours  pressing  on  the  cord,  in  "  subacute  combined 
degeneration,"  and  in  the  more  recent  patches  of  disseminated 
sclerosis,  they  are  present  in  large  numbers  in  the  tissues. 
They  make  their  way  towards  the  blood  vessels,  usually  the 
veins,  where  they  distend  the  perivascular  lymph  space,  so 
that  in  paraffin  and  celloidin  sections  it  appears  as  a  loose 
network  of  fibrous  tissue  enclosing  clear  spaces  (which  are  cell 
bodies  from  which  the  fat  has  been  dissolved)  and  dark,  some- 
what pyknotic  nuclei.  In  sections  stained  by  the  Marchi 
method  the  vessel  appears  to  be  surrounded  by  a  thick,  intensely 
black  ring.  There  is  no  doubt  that  "  compound  granular 
corpuscles  "  may  also  develop  from  cells  of  endothelial  origin, 
which  have  absorbed  the  products  of  myelin  degeneration,  and 
this  is  probably  the  origin  of  many  of  the  granular  corpuscles 
seen  in  softening  or  injuries  of  the  brain  and  cord.  On  the 
other  hand,  myelin  degeneration,  such  as  is  seen  in  ascending 
degeneration  of  the  posterior  columns,  does  not  appear  to 
produce  any  reaction  on  the  part  of  the  cells  of  the  vessel  walls, 
and  it  seems,  therefore,  unlikely  that  the  compound  granular 
corpuscles  found  in  such  a  case  are  derived  from  the  endo- 
thelium. 

According  to  Alzheimer,  cells  of  vascular  origin  have  a 
greater  power  of  fat  synthesis  than  those  possessed  by  glial 
cells.  In  support  of  this,  it  is  stated  that  the  granular  cor- 
puscles within  the  sheath  of  the  veins  stain  more  intensely 
by  the  Marchi  method  than  those  lying  free  in  the  tissues. 
Alzheimer  considers  that  in  the  granular  corpuscles  of  glial 
origin  the  lipoids  are  present  in  soluble  form,  and  that  these 
cells  do  not  pass  into  the  lymph  spaces  of  the  vessels,  but 
become  disintegrated  outside  the  perivascular  sheath.  The 
lipoid  substances  escape  and  are  absorbed  by  the  endothelial 
cells,  which  have  a  fuller  power  of  fat  synthesis,  and  elaborate 
in  their  cell  body  globules  of  fully  saturated  fat. 


30 


GENERAL  PATHOLOGY 


5.  The  Cerebro-spinal  Fluid. 

(i)  Mode  of  formation, — The  cerebro-spinal  fluid  is  formed  by 
the  choroid  plexuses  of  the  lateral,  third  and  fourth  ventricles. 
These  are  highly  vascular  protrusions  of  pia  mater  covered  over 
with  specialised  cubical  cells  derived  from  the  ependymal 
covering  of  the  ventricles.  As  to  the  manner  of  the  formation 
of  the  cerebro-spinal  fluid  there  is  still  some  controversy.  It 
was  long  regarded  as  a  secretion  similar  to  that  produced  by 


*7rf^. 


^^. 


*****    *. 


I  ''^'^^fA*^^     '^s^ 


'ft*. 


£>■  V  -■■; 


4>j^   ^Yk^ 


Fig.  8. 
Normal  choroid  plexus  from  fourth  ventricle. 


other  epithelial  structures.  In  favour  of  this  view  have  been 
cited  certain  changes  seen  in  the  cells  covering  the  plexus  during 
active  formation  of  the  fluid,  as  under  the  action  of  ether, 
and  also  the  increase  of  the  amount  of  fluid  which  results  from 
the  injection  of  various  substances  into  the  circulation.  There 
have  been  many  fallacies  in  connection  with  this  work,  as  the 
experiments  have  not  always  eliminated  factors  such  as  increase 
of  arterial  pressure  or  venous  stasis,  which,  by  increasing  the 
intracranial  contents,  would  force  more  cerebro-spinal  fluid  out 


THE  CEREBRO-SPINAL  FLUID  31 

of  the  skull.  The  results  of  Dixon  and  Halliburton,  however, 
appear  to  be  sufficiently  established.  These  authors  found  that 
extract  of  dried  choroid  plexus  had  a  very  definite  action  in 
increasing  the  amount  of  fluid  produced,  and  that  other 
cholesterin-containing  substances,  such  as  extracts  of  brain 
tissue,  had  a  similar  but  weaker  effect. 

A  different  theory  of  the  action  of  the  choroid  plexuses  was 
advanced  by  Mestrezat.  He  considered  the  cerebro-spinal 
fluid  to  be  a  product  of  dialysis  from  blood  serum,  the  choroid 
plexuses  performing  the  role  of  a  colloid  membrane.  This 
theory  is  based  on  the  similarity  in  composition  of  the  cerebro- 
spinal fluid  to  a  dialysate  from  blood  serum,  and  on  the  readiness 
with  which  any  increase  from  the  normal  in  the  percentage  of 
glucose,  chloride  or  urea  in  the  blood  shows  itself  in  an  increased 
percentage  of  these  elements  in  the  cerebro-spinal  fluid.  He 
himself  noted,  however,  that  abnormal  salts,  even  those  of 
small  molecule,  such  as  nitrates  and  iodides,  cannot  be  made 
to  pass  through  into  the  cerebro-spinal  fluid,  even  though  they 
are  administered  in  doses  large  enough  to  make  them  appear 
in  the  blood  in  considerable  amounts.  His  theory  must  there- 
fore be  qualified  to  the  extent  of  allowing  the  cells  covering  the 
choroid  plexus  a  certain  selective  action  on  the  constituents 
of  the  blood  plasma ;  and  with  this  reservation  it  appears  to  be 
in  accordance  with  the  observed  facts.  It  is  certain  that  the 
choroid  plexus  has  no  power  of  elaborating  special  enzymes 
or  protein  substances  such  as  that  possessed  by  most  secreting 
glands. 

(2)  Circulation. — The  cerebro-spinal  fluid  formed  in  the 
lateral  and  third  ventricles  passes  by  the  iter  of  Sylvius  to  the 
fourth  ventricle,  where  it  mixes  with  the  fluid  formed  by  the 
small  "plexus  quarti  ventriculi."  Thence  it  escapes  through 
the  ependymal  roof  of  the  ventricle  by  the  central  foramen  of 
Magendie  and  the  two  lateral  foramina  of  Luschka,  all  of 
which  are  usually  present.  It  passes  directly  into  the  cisterna 
magna,  and  thence  diffuses  both  downwards  in  the  subarach- 
noid space  surrounding  the  cord,  and  upwards  by  the  pontine 
and  basal  cisterns  and  the  cisterns  of  the  Sylvian  fissure.  Over 
the  cortex  of  the  brain  the  arachnoid  membrane  is  fairly  closely 
applied  to  the  pia  mater,  but  it  bridges  over  the  sulci,  and  along 
the  channels  thus  formed  the  cerebro-spinal  fluid  gains  access 


32  GENERAL  PATHOLOGY 

to  the  large  venous  sinuses  and  lacunae,  which  form  its  chief 
means  of  escape  into  the  blood  stream.  In  relation  to  these 
there  are  developed  arachnoid  villi,  the  larger  of  which  in 
relation  to  the  superior  longitudinal  sinus  have  been  termed 
Pacchionian  granulations.  In  addition  to  the  superior  longi- 
tudinal sinus  and  its  lateral  lacunae,  Key  and  Retzius  found 
such  villi  in  relation  to  the  transverse  sinus,  the  cavernous 
sinus,  the  superior  petrosal  sinus  and  the  middle  meningeal 
veins.  The  conception  of  their  structures  formed  by  these 
authors  is  that  they  are  composed  of  an  inner  core  consisting 
of  a  meshwork  of  arachnoid  tissue,  both  lined  and  covered  by 
endothelium.  This  is  separated  from  the  wall  of  the  sinus  into 
which  it  projects  by  a  continuation  of  the  subdural  space,  so 
that  the  villus  can  be  dislodged  from  its  nest  in  the  wall  of  the 
sinus  by  injection  of  fluids  into  the  subdural  space,  without  a 
hole  being  made  in  the  wall  of  the  sinus.  According  to  this 
view,  between  the  cerebro-spinal  fluid  and  the  blood  in  the 
sinus  there  are  four  thin  endothelial  layers.  Key  and  Retzius 
considered  that  stomata  were  present  between  the  cells, 
allowing  for  the  free  passage  of  the  cerebro-spinal  fluid  into 
the  sinus,  but  of  these  there  is  no  evidence. 

There  are  several  important  prolongations  of  the  subarach- 
noid space,  such  as  the  funnel-shaped  sheaths  round  the  cranial 
nerves,  which  are  especially  important  in  relation  to  the  optic 
nerves  and  the  auditory  nerves.  By  means  of  the  latter  the 
cerebro-spinal  fluid  communicates  freely  with  the  perilymph 
of  the  internal  ear.  Scarcely  less  important  is  the  Virchow- 
Robin  space,  which  surrounds  both  arteries  and  veins  as  they 
enter  and  leave  the  brain,  and  is  continued  along  them  right 
up  to  the  capillaries.  Its  walls  appear  to  be  derived  from  the 
pia  mater,  and  it  communicates  directly  with  the  lymph  chan- 
nels in  the  pia,  and  through  these  with  the  subarachnoid  space. 
It  may  thus  be  injected  from  the  subarachnoid  space,  and 
virtually  forms  a  prolongation  of  the  space  into  the  substance 
of  the  brain  and  cord. 

The  arachnoid  is  covered  with  endothelium,  both  internally 
and  externally,  so  that  between  the  subarachnoid  and  subdural 
spaces  there  are  two  distinct  layers  of  endothelium  which 
normally  form  an  efficient  barrier  against  the  passage  of  fluids 
from  one  to  the  other.     It  must  be  remembered  that  in  the 


CEREBRO-SPINAL  FLUID  33 

normal  condition  there  is  no  cerebro-spinal  fluid  in  the  subdural 
space,  which  is,  in  fact,  only  a  potential  space  containing  a 
very  thin  film  of  lymph. 

The  amount  of  cerebro-spinal  fluid  which  can  be  formed  in 
twenty-four  hours  may  rise  to  one  or  two  litres  when  there  is 
free  escape.  In  the  human  subject  under  normal  conditions 
there  are  probably  from  60  to  80  c.c.  of  cerebro-spinal  fluid,  of 
which  only  a  very  small  proportion  is  present  in  the  ventricles, 
the  larger  part  lying  in  the  subarachnoid  space  around  the 
cord  and  in  the  cisterns  at  the  base  of  the  brain.  It  has  been 
calculated  that  it  is  renewed  completely  six  or  seven  times 
a  day. 

The  pressure  of  the  cerebro-spinal  fluid  in  the  lumbar  theca 
in  man  varies  normally  from  60  to  120  mm.  of  water  in  the 
recumbent  position.  It  may  be  raised  much  above  this  in 
pathological  conditions.  It  seems  to  correspond  very  closely 
to  the  pressure  in  the  large  venous  sinuses  of  the  brain,  especially 
the  torcular  Herophili.  Both  the  arterial  pulse  and  the  altera- 
tion in  venous  pressure  due  to  respiration  affect  the  cerebro- 
spinal fluid,  so  that  it  undergoes  a  perpetual  to  and  fro 
movement.  This  probably  has  a  great  effect  in  hastening  its 
absorption  and  in  promoting  free  renewal  of  the  fluid  which 
surrounds  the  spinal  cord.  It  is  a  common  enough  observa- 
tion that  a  forcible  expiratory  effort  such  as  coughing,  or, 
in  infants,  crying,  raises  the  pressure  of  the  cerebro-spinal 
fluid  remarkably. 

(3)  Mode  of  absorption. — Absorption  of  the  fluid  into  the 
circulation  takes  place  by  two  main  routes.  First  aind  more 
important  is  the  venous  route,  especially  by  means  of  the 
arachnoid  villi.  It  is  not  unlikely  that  there  is  also  a  consider- 
able absorption  by  the  adventitial  sheaths  of  the  veins,  but 
this  is  probably  very  small  as  compared  with  the  escape  into 
the  larger  venous  sinuses.  The  other  route  is  along  the  peri- 
neural lymph  spaces,  and  in  the  spinal  theca  this  probably 
constitutes  the  chief  means  of  escape.  Lymph  spaces  are  more 
than  usually  abundant  around  the  olfactory  nerves,  and  accord- 
ing to  Mestrezat  and  others  the  olfactory  mucous  membrane 
is  freely  bathed  with  cerebro-spinal  fluid.  But  it  is  probable 
that  under  normal  conditions  the  lymph  current  runs  as 
much  up  as  down  the  nerves,  and  that  what  cerebro-spinal 

3 


34  GENERAL  PATHOLOGY 

fluid  escapes  by  this  route  is  replaced,  at  least  partially,  by 
lymph. 

Various  experiments  have  been  done  to  find  out  the  relative 
importance  of  these  two  routes.  Leonard  Hill  found  that 
methylene-blue  injected  into  the  theca  appeared  in  the  urine 
in  from  ten  to  twenty  minutes,  but  was  not  visible  in  the 
lymphatics  of  the  neck  till  after  an  hour.  Even  more  direct 
are  the  observations  of  Weed  that  dye-stuffs  introduced  into 
the  spinal  theca  when  this  was  ligated  at  its  upper  end  did  not 
appear  in  the  urine  until  after  seventy-five  minutes,  and  then 
in  minute  traces  only,  whereas,  with  the  theca  intact,  they 
appeared  in  the  urine  in  twenty  minutes.  In  another  series  of 
experiments  he  injected  dye-stuffs  into  the  cerebellar  cistern, 
and  found  that  there  was  no  difference  in  the  proportion  of  the 
dye  recovered  from  the  urine  in  two  hours,  whether  the  spinal 
theca  was  ligated  off  or  left  intact.  This  experiment  shows 
that  under  normal  conditions  of  pressure  the  escape  of  cerebro- 
spinal fluid  along  the  spinal  nerve  roots  is  minimal. 

(4)  Relation  of  the  cerebrospinal  fluid  with  the  nerve  centres. — 
The  free  communication  which  exists  between  the  subarachnoid 
space  and  the  adventitial  (Virchow-Robin)  space  of  the  cerebral 
and  spinal  vessels  has  already  been  mentioned.  In  all  cases  of 
meningitis  and  meningeal  infiltration  this  space  is  found  dis- 
tended with  leucocytes  or  small  round  cells  for  a  considerable 
distance  into  the  substance  of  the  brain,  especially  along  the 
larger  vessels.  Mott  has  suggested  that  the  relation  of  the 
cerebro-spinal  fluid  with  the  nerve  cells  does  not  end  here, 
but  that  by  means  of  the  so-called  perivascular  space  of  His 
it  gains  access  directly  through  fine  lymph  spaces  to  the  space 
of  Obersteiner  surrounding  the  nerve  cells  so  that  these  are 
actually  bathed  in  cerebro-spinal  fluid.  There  is  general 
agreement  that  the  original  description  of  these  spaces  as  lined 
with  endothelium  is  wrong,  and  doubts  have  been  cast  on  their 
existence  under  normal  conditions.  But  whether  they  exist 
or  not  it  is  clear  that  some  fluid,  either  lymph  or  cerebro-spinal 
fluid,  can  find  its  way  through  the  meshes  of  the  glia  to  the 
nerve  cells.  Weed,  using  ferro-cyanide  injections  into  the 
subarachnoid  space,  found  that  some  of  the  nerve  cells  were 
ringed  round  with  granules  of  Prussian  blue.  It  seems  therefore 
likely  that,  under  some  conditions,  either  by  increase  of  the 


CEREBRO-SPINAL  FLUID  35 

cerebro-spinal  fluid  pressure,  or  by  diminution  of  the  capillary 
pressure  (as  in  Mott's  experiments,  where  the  carotid  artery 
was  tied),  the  cerebro-spinal  fluid  can  penetrate  pretty  freely 
into  the  nervous  tissue.  There  are,  however,  several  arguments 
against  its  doing  so,  at  any  rate,  to  any  considerable  degree, 
under  normal  conditions.  In  the  first  place,  the  Virchow- 
Robin  space  seems  in  normal  histological  preparations  to  be 
empty;  and  Bruce's  work  on  degenerative  conditions  of  the 
nerve  elements,  in  which  this  space  becomes  filled  with 
scavenger  cells,  indicates  that  the  current  is  chiefly  from  within 
outwards — that  is,  from  the  smaller  to  the  larger  vessels.  Teale 
and  Embleton  have  found  that  tetanus  antitoxin  introduced 
into  the  subarachnoid  space,  after  tetanic  symptoms  had  been 
produced  by  the  injection  of  tetanus  toxin,  has  no  effect  in 
reducing  the  spasms.  It  appears  therefore  that  foreign  proteids, 
at  any  rate,  cannot  pass  from  the  subarachnoid  space  to  the 
nerve  cells.  They  have  also  shown  that  horse  serum  does  not 
pass  out  into  the  brain  tissue  from  the  capillaries,  although 
it  passes  out  into  the  tissues  of  the  liver,  spleen  and  omentum. 
This  may  be  due  to  the  walls  of  the  brain  capillaries  having  a 
power  of  selective  filtration  similar  to  that  exercised  by  the 
choroid  plexus.  Various  mechanisms  may  thus  be  at  work  to 
prevent  the  sensitive  nerve  cells  from  attack  by  proteid  and 
other  poisons. 

(5)  Function. — The  chief  functions  of  the  cerebro-spinal 
fluid  are: 

(i.)  To  form  a  water  cushion  protecting  the  brain  and  cord 
from  any  sudden  shock.  The  spinal  cord  is  so  suspended  in  this 
fluid  by  its  ligaments  that  in  health  it  probably  never  comes  in 
contact  with  its  bony  envelope. 

(ii.)  As  a  reservoir  to  regulate  the  contents  of  the  cranial 
cavity.  When  the  brain  substance  increases  or  vascular 
congestion  is  present  the  cerebro-spinal  fluid  ebbs  away.  When 
the  brain  shrinks,  more  cerebro-spinal  fluid  is  formed  to  fill  the 
vacant  space.  This  is  well  seen  in  general  paralysis  of  the 
insane. 

(iii.)  It  serves  to  wash  away  the  products  of  tissue  metabo- 
lism, and  it  may  provide  pabulum  for  the  nourishment  of  the 
nerve  cells. 

(6)  Normal  composition. — The  cerebro-spinal  fluid  is  a  clear 


36 


GENERAL  PATHOLOGY 


watery  fluid  of  low  specific  gravity  (about  1007-5),  and  con- 
taining only  a  very  few  lymphocytes  in  suspension  (less  than 
5  per  c.mm.).  It  contains  a  small  quantity  of  albumen,  which 
normally  does  not  exceed  0*03  per  cent.  This  is  made  up  of 
both  serum  albumen  and  serum  globulin,  with  a  preponderance 
of  globulin.  Glucose  is  present  to  the  extent  of  about  o  05  per 
cent.,  and  is  fairly  constant  at  this  level.  The  chlorides,  which 
are  mainly  sodium  and  potassium  salts,  form  a  remarkably 
constant  ingredient.  Their  proportion  of  073  per  cent,  is 
extraordinarily  steady  in  health,  and  variations  below  070  per 
cent.,  or  above  076  per  cent.,  may  be  regarded  as  indications 
of  disease.  Urea  is  normally  present,  but  varies  considerably 
in  quantity.  The  normal  percentage  is  given  as  from  0*003 
per  cent,  to  o  01  per  cent.  In  addition,  the  fluid  contains 
traces  of  bicarbonates,  phosphates,  sulphates,  calcium,  and 
magnesium,  and  minute  traces  of  nitrates.  Its  alkalinity  is 
similar  to  that  of  blood  serum  both  as  regards  H-ion  concentra- 
tion and  alkaline  reserve.  It  is  normally  alkaline  to  litmus, 
and  acid  to  phenolphthalein  (Levinson) . 

The  following  table  is  taken  from  Mestrezat,  who  compiled 
it  from  an  analysis  of  fluids  removed  from  healthy  patients 
prior  to  stovaine  anaesthesia: 


Normal  Mean. 

Normal  Variations. 

Specific  gravity    .  . 

1007-6 

1007-3-1008 

Freezing-point 

.  . 

-0-576°  c. 

-o-57°-o-59°C. 

Alkalinity     of     the     ash 

(in    Na2C03 

percentage) 

0-125 

0-120-0-137 

Albumens  (percentage)  .  . 

.  . 

0-018 

0-013-0-030 

Glucose 

. . 

0-053 

0-048-0-058 

Chlorides 

. . 

0.732 

0-725-0-740 

Urea 

.. 

o-oo6 

0-003-0-010 

(7)  Pathological  alterations  in  the  cerebrospinal  fluid.  — 
Although  the  most  striking  changes  met  with  in  the  cerebro- 
spinal fluid  are  due  to  disease  of  the  cerebro-spinal  nervous 
system  or  its  coverings,  it  must  not  be  forgotten  that  certain 
general  diseases  may  affect  the  composition  of  the  fluid.  These 
are  the  more  important  as  in  them  the  fluid  is  altered  at  its 
source,  and  that  obtained  by  lumbar  puncture  is  almost  exactly 
similar  to  the  ventricular  fluid. 


CEREBRO-SPINAL  FLUID  37 

The  chief  general  disorders  which  produce  definite  effects 
on  the  cerebro-spinal  fluid  are  those  where  the  normal  propor- 
tion of  the  constituents  of  the  blood  plasma  are  changed,  as  in 
diabetes  mellitus  and  the  various  forms  of  nephritis.  The 
cerebro-spinal  fluid  is  extremely  sensitive  to  changes  in  the 
chemical  composition  of  the  blood  plasma,  and  a  raised  per- 
centage of  sugar,  chloride,  or  urea  in  the  blood  will  at  once  show 
itself  in  the  cerebro-spinal  fluid.  The  ease  with  which  the 
exact  percentages  of  these  substances  may  be  estimated  make 
examination  of  the  cerebro-spinal  fluid  of  such  cases  a  valuable 
aid  in  diagnosis  and  prognosis.  Other  diffusible  substances, 
such  as  alcohol,  acetone  and  formaldehyde,  pass  readily  into 
the  cerebro-spinal  fluid. 

Apart  from  these  diseases  and  the  cases  where  arterio- 
sclerotic changes  have  impaired  the  efliciency  of  the  choroid 
plexus,  it  may  be  assumed  that  the  fluid  as  secreted  has  a 
fairly  constant  chemical  composition.  Whether  it  actually 
contains  albumen  and  cells  is  a  matter  of  conjecture,  but  other- 
wise it  probably  differs  little  from  that  obtained  by  lumbar 
puncture.  Alterations  from  the  normal  may  take  place  in  its 
course  from  the  choroid  plexus  to  the  lumbar  theca,  and  are 
therefore  most  likely  to  occur  when  either  the  walls  of  the 
ventricles,  or  the  subarachnoid  space  surrounding  the  base  of 
the  brain  and  cord,  are  the  seat  of  disease. 

(a)  Appearance. — Normal  cerebro-spinal  fluid  is  perfectly 
clear  and  colourless,  like  water.  This  appearance  may  be 
preserved  in  spite  of  considerable  pathological  increase  both 
in  the  number  of  lymphocytes  and  the  albumen  content. 
Where  a  very  considerable  lymphocytosis  is  present  the  fluid 
may  present  to  the  naked  eye  a  very  slight  turbidity  or  opales- 
cence, which  can  only  be  seen  on  examining  the  fluid  in  a  good 
light  against  a  black  background.  It  is  sometimes  impossible 
to  distinguish  this  turbidity  from  that  produced  by  a  very 
slight  blood  admixture,  but  the  difference  is  at  once  ap- 
parent on  centrifugalisation,  as  in  the  latter  case  the  deposit 
is  definitely  red. 

An  apparently  clear  fluid  which  on  standing  yields  a  fine 
web  of  coagulum  is  characteristic  of  tubercular  meningitis. 
A  similar  appearance  may  be  given  in  post-basic  meningitis, 
in  poliomyelitis  and  in  some  acute  cases  of  syphilitic  meningitis. 


38  GENERAL  PATHOLOGY 

In  these  conditions  the  fluid  may  show  a  very  faint  yellow  tint, 
only  seen  on  looking  down  the  long  axis  of  the  tube;  this  is 
most  frequently  seen  in  tubercular  meningitis.  In  more  acute 
forms  of  meningitis  the  turbidity  is  much  more  obvious,  and 
the  fluid  may  become  completely  opaque  with  pus.  Such 
fluids  also  coagulate  into  a  finer  or  heavier  coagulum  after 
being  withdrawn,  and  often  show  a  yellowish  or  greenish  dis- 
coloration. 

Blood  admixture  may  be  due  to  damage  to  a  vessel  at  the 
time  of  the  lumbar  puncture,  or  to  intraventricular  or  sub- 
arachnoid haemorrhage.  In  the  former  case  the  amount  of  blood 
admixture  is  not  constant,  and  if  the  fluid  is  received  into  a 
series  of  tubes  some  will  be  more  and  others  less  blood-stained. 
Centrifugalisation  in  this  case  will  yield  a  colourless  fluid 
unless  the  blood  is  present  in  large  amounts.  When  the  blood 
was  present  in  the  subarachnoid  space  before  lumbar  puncture 
the  fluid  is  evenly  tinged,  and  if  the  blood  has  been  present  for 
more  than  one  or  two  days  there  will  be  a  yellow  coloration  of 
the  fluid  due  to  disintegration  of  the  red  blood  corpuscles  and 
alteration  of  the  haemoglobin.  For  the  first  two  or  three  days 
after  such  a  haemorrhage  many  red  blood  corpuscles  are  still 
present  in  a  yellowish  fluid.  A  few  days  later  the  fluid  becomes 
clear,  but  of  a  darker  yellow  colour,  which  gradually  disappears 
in  the  course  of  one  or  two  weeks. 

An  alteration  in  the  appearance  of  the  fluid  is  also  frequently 
present  in  the  loculation  syndrome  first  described  by  Froin  (p.  43) . 
The  colour  may  vary  from  a  pale  straw  to  a  deep  greenish 
tan.  It  may  also  coagulate  either  spontaneously  or  after  the 
addition  of  a  drop  of  fresh  blood.  In  the  more  pronounced 
cases  the  fluid  may  coagulate  en  masse  so  that  on  inversion  of 
the  tube  no  fluid  escapes,  and  such  fluids  by  coagulating  in  the 
needle  may  completely  arrest  the  flow  of  cerebro-spinal  fluid. 
Frequently,  however,  only  a  fine  web-like  coagulum  results. 
The  actual  colour  is  usually  identical  with  that  resulting  from 
haemorrhage  into  the  subarachnoid  space,  and  it  is  only  by  a 
further  examination  of  the  fluid  that  its  cause  can  be  identified. 

[h)  Cells. — So  long  as  all  the  factors  influencing  the  passage 
of  cells  into  the  cerebro-spinal  fluid  are  not  definitely  known,  it 
is  impossible  to  dogmatise  as  to  the  number  of  cells  normally 
present,   especially  as  the  majority  of  cerebro-spinal  fluids 


CEREBRO-SPINAL  FLUID  39 

examined  come  from  patients  with  some  disease  either  of  a 
degenerative  or  inflammatory  nature  in  their  brain  or  cord. 
The  examination  of  a  very  large  number  of  fluids  by  many 
competent  observers  has  given  rise  to  a  general  consensus  of 
opinion  that,  apart  from  disease  of  the  cerebro-spinal  axis,  the 
number  of  cells  present  never  exceeds  5  per  c.mm.*  Except 
for  the  occasional  presence  of  one  of  the  endothelial  cells  lining 
the  arachnoid,  these  are  all  of  the  small  lymphocyte  type. 

It  is  of  as  great  diagnostic  importance  to  find  abnormal 
types  such  as  large  mononuclear  or  polymorphonuclear  cells 
as  to  find  an  excess  in  the  total  number  of  cells.  Such 
abnormal  cells,  even  though  they  do  not  exceed  5  per  c.mm., 
may  have  great  diagnostic  significance  in  cases  of  intracranial 
disease,  as  a  few  large  mononuclear  cells  are  often  found  in 
cases  of  tumour  involving  the  meninges  or  invading  the  walls 
of  the  ventricles,  whereas  a  few  polymorphonuclear  and  phago- 
cytic cells  may  be  present  when  a  brain  abscess  lies  in  close 
relation  to  the  meninges. 

A'^lymphocytic  increase  is  usually  present  in  all  forms  of 
syphilitic  disease  of  the  meninges,  as  also  in  tabes  and  general 
paralysis.  Any  figure  up  to  200  or  500  per  c.mm.  may  be 
reached,  but  those  between  10  and  50  are  most  common.  In 
these  conditions  larger  forms  of  mononuclear  cells  are  con- 
stantly present  in  smaller  or  larger  percentages,  and  plasma 
cells  are  not  uncommon. 

A  lymphocytic  increase  is  also  present  in  certain  other  acute 
or  subacute  diseases,  notably  in  herpes  zoster  and  disseminated 
sclerosis.  In  lethargic  encephalitis  the  fluid  may  contain  no 
increase  of  cells,  or  a  considerable  mononuclear  increase  may  be 
present.  Poliomyelitis  and  polio-encephalitis,  during  the  acute 
stage,  usually  give  rise  to  a  considerable  cell  increase  up  to 
40  or  50  per  c.mm.,  consisting  chiefly  of  mononuclear  with  a 
small  proportion  of  polymorphonuclear  cells. 

Tubercular  meningitis  is  characterised  by  a  very  considerable 
rise  in  cells,  which  may  be  almost  wholly  lymphocytes,  or  may 

*  It  is  sometimes  stated  in  textbooks  that  the  number  of  cells  may  normally 
rise  to  10  or  even  20  per  c.mm.  This  is  almost  certainly  an  error  and  prob- 
ably arises  either  from  faulty  technique,  e.g.  estimating  from  the  number 
of  cells  present  in  ^  c.mm.,  or  from  films  made  after  centrifugalising  the  fluid, 
or  from  neglecting  the  presence  of  some  inflammatory  or  degenerative  disease 
of  the  cerebro-spinaFsystem. 


40  PROTEINS  IN 

show  a  considerable  proportion,  up  to  50  per  cent.,  of  poly- 
morphonuclear cells.  This  proportion  does  not  seem  to  bear 
any  relation  either  to  the  acuteness  or  to  the  stage  of  the 
disease,  but  is  usually  higher  in  children  than  in  adults. 

Acute  meningitis  due  to  pyogenetic  organisms  always  leads 
to  an  enormous  increase  of  cells,  the  great  majority  of  which 
are  polymorphonuclear.  Along  with  these  there  is  usually  a 
small  proportion  of  large  phagocytic  mononuclear  cells.  In 
this  as  in  the  tubercular  form  the  causal  organism  may  be 
seen  in  stained  films  either  free  or  within  the  cells. 

Finally,  in  all  degenerative  conditions  of  the  brain  or  cord, 
compound  granular  corpuscles  may  make  their  way  into  the 
cerebro-spinal  fluid  along  the  Virchow-Robin  space  of  the  veins. 

(c)  The  albuminous  substances  are  subject  to  great  variations. 
As  a  general  rule,  in  diseases  other  than  syphilitic  disease  of 
the  nervous  system  the  chief  increase  is  in  the  serum  albumen. 
In  syphilitic  disease  the  serum  globulin  also  rises  in  percentage 
to  a  considerable  degree,  though  never  to  the  same  extent 
as  the  serum  albumen.  Herein  lies  the  advantage  of  com- 
bining an  estimation  of  the  total  albumen  with  the  Nonne- 
Apelt  or  Noguchi  reaction.  If  this  is  not  done  the  observer 
may  be  led  astray  by  various  non-syphilitic  conditions  which 
give  a  positive  globulin  reaction,  along  with  a  considerable 
increase  in  the  total  albumens  and  in  the  cellular  elements. 
If,  on  the  other  hand,  a  positive  globulin  reaction  is  obtained 
from  a  fluid  with  a  total  albumen  content  of  less  than  0*04  per 
cent.,  there  is  a  strong  presumption  that  the  case  is  syphilitic. 

In  acute  tubercular  meningitis  the  albumen  may  rise  to  0*2 
per  cent,  or  even  higher.  It  is  apt  to  be  rather  higher  in  adults 
than  in  children.  Meningococcal  meningitis  gives  especially 
high  albumen  percentages,  0*3  per  cent,  being  common  and 
0*6  to  0*8  per  cent,  not  very  unusual.  In  meningeal  inflamma- 
tion due  to  other  organisms  the  albumen  content  usually  does 
not  rise  above  0*2  per  cent. 

In  all  these  acuter  forms  of  meningitis  fibrinogen  is  present, 
so  that  a  coagulum  forms  in  the  tube  soon  after  the  fluid  is 
withdrawn.  This  constitutes  a  very  valuable  diagnostic  sign 
in  tubercular  meningitis,  and  should  always  be  examined  for 
when  the  fluid  appears  to  be  almost  clear.  It  may  be  missed 
if  the  fluid  is  shaken  about  after  withdrawal. 


CEREBRO-SPINAL  FLUID  41 

In  most  cases  of  subacute  meningitis,  syphilitic  or  otherwise, 
the  percentage  of  albumen  does  not  rise  above  o-i  per  cent.  In 
syphilitic  meningitis,  quite  apart  from  the  "  syndrome  of 
Froin,"  fibrinogen  may  sometimes  be  found  in  the  acuter 
stages  of  the  disease.  Fibrinogen  may  be  present  in  sufficient 
quantity  to  give  rise  to  a  fine  coagulum  without  any  very  great 
rise  in  the  quantity  of  albumen.  This  is  most  frequently  the 
case  in  poliomyelitis  and  polio-encephalitis,  in  which  fibrinogen 
may  be  present  for  several  weeks  after  the  onset  of  the  disease. 

In  acute  polyneuritis  the  albumen  content  may  be  raised 
to  O'l  per  cent,  or  over.  This  may  be  due,  as  Mestrezat 
considers,  to  an  accompanying  inflammation  of  the  nerve  cells 
of  the  ventral  cornua  and  dorsal  root  ganglia — a  so-called 
neuronitis.  It  is  also  probably  due,  in  part  at  least,  to  the 
addition  of  lymph  which  has  passed  up  the  lymphatics  of  the 
inflamed  nerves  into  the  subarachnoid  space.  This  addition 
of  albumen  will  be  the  more  evident  in  the  cerebro-spinal  fluid 
drawn  off  from  the  lumbar  theca  in  that  it  reaches  the  sub- 
arachnoid space  chiefly  along  the  large  roots  of  the  lumbo- 
sacral plexus. 

In  certain  cases  of  cerebral  oedema,  as  in  uraemia,  there  is 
a  definite  rise  in  the  albumen  content  of  the  cerebro-spinal 
fluid,  but  except  for  this  it  is  seldom  increased  by  diseases 
which  do  not  primarily  affect  the  cerebro-spinal  nervous  system. 

The  greatest  increase  in  the  percentage  of  albumen  is  seen 
in  Froin's  loculation  syndrome,  where  readings  above  i  per 
cent,  are  by  no  means  infrequent. 

Kafka  has  applied  to  the  examination  of  the  cerebro-spinal 
fluid  the  method  of  salting  out  the  different  globulin  fractions 
by  different  degrees  of  saturation  with  ammonium  sulphate. 
He  finds  that  a  precipitation  of  globulin  is  given  by  28  per  cent, 
saturation  in  acute  meningitis,  by  33  per  cent,  saturation  in 
general  paralysis,  and  by  40  per  cent,  in  lues  cerebri.  These 
percentages  indicate  the  presence  of  fibrinogen  in  acute  menin- 
gitis (and  also  occasionally  in  the  more  acute  forms  of  syphilitic 
meningitis),  of  euglobulin  in  general  paralysis,  and  of  pseudo- 
globulin  in  lues  cerebri. 

According  to  Mestrezat,  the  normal  cerebro-spinal  fluid 
contains  rather  more  globulin  than  serum  albumen.  But  in 
all  forms  of  inflammation  of  the  meninges  the  serum  albumen 


42  CHEMICAL  CHANGES  IN 

appears  in  the  cerebro-spinal  fluid  in  far  greater  quantity  than 
the  serum  globuHn,  the  proportions  ranging  from  i:  6  to  i:  8. 
When,  however,  the  choroid  plexus  becomes  diseased  and  its 
function  of  selective  filtration  is  lost,  globulin  may  pass  into 
the  cerebro-spinal  fluid  in  much  greater  amounts,  and  the 
proportion  of  globulin  to  albumen  may  rise  to  i :  2.  Similarly 
in  the  increase  of  proteid  shown  by  loculated  fluids,  globulin 
may  bear  a  proportion  to  albumen  of  1^3.  Eskuchen  gives 
the  proportion  of  globulin  to  albumen  in  cerebro-spinal  lues 
as  1 :  12,  and  in  general  paralysis  3:7. 

(d)  Glucose. — The  percentage  of  glucose  in  the  cerebro-spinal 
fluid  may  be  increased  or  reduced.  Of  the  factors  leading  to 
increased  percentages  the  most  important  is  excess  of  glucose 
in  the  blood  (hyperglycaemia) .  In  diabetes  mellitus  the 
amount  in  the  cerebro-spinal  fluid  is  constantly  above  o*i  per 
cent.  It  is  also  above  normal  in  all  acute  infective  diseases 
or  intoxications  associated  with  a  general  polymorphonuclear 
leucocytosis.  This  is  probably  due  to  the  power  which  these 
cells  possess  of  carrying  glycogen  to  the  tissues.  An  increase 
is  usually  found  in  cases  of  increased  intracranial  pressure, 
even  during  the  initial  stages  of  tubercular  meningitis.  The 
cause  of  this  is  obscure,  but  it  may  be  due  to  the  effects  of 
pressure  on  the  pituitary  gland. 

The  percentage  of  glucose  is  reduced  in  all  cases  of  meningeal 
inflammation,  whether  acute,  subacute  or  chronic.  In  acute 
meningitis  the  small  amount  of  glucose  that  may  be  present 
when  the  fluid  is  newly  drawn  may  disappear  from  the  fluid  in 
a  few  hours.  This  is  due  chiefly  to  the  avidity  with  which 
bacteria  use  glucose  as  a  food  and  also  to  some  extent  to 
the  power  which  polymorphonuclear  leucocytes  possess  of 
absorbing  it.  Glucose  is  also  reduced  in  cases  of  subarachnoid 
haemorrhage  from  any  cause. 

As  will  be  seen  later  in  dealing  with  the  loculation  syndrome, 
a  fluid  which  contains  no  bacteria  and  only  an  extremely 
small  number  of  polymorphonuclear  cells  may  have  its  glucose 
reduced  if  it  lies  close  to  an  area  of  meningeal  inflammation. 
In  such  cases  a  process  of  diffusion  must  be  supposed  to  take 
place  between  the  loculated  sugar-containing  fluid  and  the 
purulent  sugar- free  cerebro-spinal  fluid  above  it. 

In  all  cases  of  meningitis  there  is,  along  with  the  diminution 


CEREBRO-SPINAL  FLUID  43 

of  glucose,  a  diminution  of  the  alkalinity  of  the  fluid  due  to  the 
formation  of  organic  acids. 

(e)  Chlorides. — The  constant  level  (0*70  to  0*76  per  cent.) 
to  which  the  chlorides  in  the  cerebro-spinal  fluid  normally 
keep  makes  their  estimation  one  of  the  most  useful  parts 
of  the  examination  of  the  fluid.  The  indications  which  ab- 
normal percentages  give  are  also  very  plain  and  straight- 
forward. A  raised  percentage  of  chlorides  is  always  an  indi- 
cation of  renal  inadequacy  ;  a  slightly  lowered  percentage 
(from  0*68  to  0'70  per  cent.)  is  an  indication  either  of  an  acute 
general  infection  or  of  slight  meningitis.  Figures  below 
0*68  per  cent,  are  indicative  of  grave  meningeal  infection. 

The  only  condition  in  which  percentages  below  0*6  per  cent, 
are  found  is  tubercular  meningitis.  This  point  is  emphasised 
by  Mestrezat,  who  regards  it  as  of  a  pathognomonic  significance 
second  only  to  the  discovery  of  the  tubercle  bacillus  in  the 
cerebro-spinal  fluid.  It  is  due  in  part  to  the  reduction  of  the 
chlorides  in  the  blood,  which  occurs  in  acute  general  tuber- 
culosis, and  partly  to  a  local  action  of  the  bacilli  in  the  sub- 
arachnoid space  on  the  chlorides  in  the  cerebro-spinal  fluid. 
The  chloride  percentage  may  not,  however,  be  reduced  in  the 
early  stages  of  the  disease. 

(/)  Urea. — The  chief  importance  of  the  urea  in  the  cerebro- 
spinal fluid  is  in  relation  to  uraemia.  But  in  meningitis  or 
wherever  there  is  an  abnormally  free  passage  of  lymph  into  the 
cerebro-spinal  fluid  the  urea  is  increased,  as  also  in  many 
degenerative  conditions  of  the  cerebro-spinal  axis.  Any 
reading  above  0*05  per  cent,  with  a  normal  albumen  content  is 
indicative  of  renal  inadequacy.  In  uraemia  the  percentages 
run  higher.  Mestrezat  states  that  cases  with  a  percentage  of 
0*3  are  uniformly  fatal. 

(g)  Loculation  syndrome  (Syndrome  of  Froin). — When  for  any 
reason  the  cerebro-spinal  fluid  is  shut  off  completely,  or  almost 
completely,  from  access  to  the  lower  part  of  the  spinal  theca, 
the  fluid  obtained  by  lumbar  puncture  is  altered  in  certain 
definite  ways.  The  chief  is  a  great  increase  in  the  proteid  con- 
tent, both  albumen  and  globulin  being  represented  in  propor- 
tions approximating  to  those  in  which  they  occur  in  the  blood 
serum.  Frequently,  and  in  well-established  cases  constantly, 
the  fluid  acquires  a  yellow  tint,  varying  from  the  palest  straw 


44  CEREBRO-SPINAL  FLUID 

colour,  only  visible  on  looking  down  the  long  axis  of  the  tube, 
to  a  dark  greenish-tan  colour  resembling  that  of  the  urine  in 
jaundice.  Along  with  these  changes  fibrinogen  is  almost 
always  present,  and  sometimes  causes  the  fluid  to  coagulate 
spontaneously  in  the  test-tube  as  soon  as  it  is  withdrawn, 
but  if  cellular  elements  are  scanty  it  may  be  necessary  to  add 
a  drop  of  fresh  blood,  thus  providing  fibrin  ferment,  in  order 
to  produce  this  coagulation.  A  yellow  fluid  coagulating 
spontaneously  within  a  few  seconds  of  withdrawal  from  the 
body  gives  a  typical  picture  of  the  syndrome  described  by 
Froin  in  1903.  In  addition  to  the  above-mentioned  changes 
which  give  it  its  characteristic  appearance,  it  may  show 
other  abnormalities  of  which  the  most  important  is  the 
presence  of  albumoses  and  peptones  due  to  the  autolysis  of 
albumens,  so  that  the  fluid  may  give  a  typical  biuret  reaction 
after  removal  of  the  albumen.  This  is  only  found  in  the  more 
pronounced  cases.  The  percentage  of  glucose  is  usually  in- 
creased slightly,  and  the  urea  percentage  may  be  considerably 
increased.  The  cell  content  and  the  chloride  content  are 
frequently  normal,  but  these  depend  entirely  on  the  cause  of 
the  loculation  of  the  fluid.  Where  it  is  due  to  syphilitic  menin- 
gitis the  cells  may  be  very  greatly  increased  and  a  considerable 
percentage  of  large  mononuclear  cells  may  be  present.  Usually 
the  chlorides  are  slightly  reduced  (in  the  neighbourhood  of 
0*7  per  cent.),  but  when  the  loculation  is  due  to  some  acute 
inflammation,  e.g.  acute  myelitis  or  meningitis,  they  may  be 
considerably  reduced. 

The  most  important  part  of  the  syndrome  undoubtedly  is 
the  high  albumen  content,  and  it  may  be  laid  down  as  a  rule 
that  any  cerebro-spinal  fluid  containing  i  per  cent,  albumen 
or  over  is  shut  off  from  communication  with  the  ventricular 
system.  But  with  very  much  lower  albumen  percentages,  and 
in  the  absence  of  any  yellow  coloration,  there  may  be  a 
strong  presumption  that  we  are  dealing  with  the  loculation 
syndrome  if  the  number  of  cells  and  the  percentages  of  the 
other  constituents  of  the  fluid  are  normal.  Such  fluids  are 
often  found  in  cases  of  spinal  tumour.  Pott's  disease  or  arach- 
noid cyst  where  the  communication  between  the  ventricles  and 
the  lumbar  theca  is  not  completely  obliterated.  The  highest 
albumen   percentages   we  have  personally  encountered,  e.g. 


SYNDROME  OF  FROIN  45 

2  per  cent.,  2*5  per  cent.,  and  3  per  cent.,  have  been  in  cases  of 
acute  myelitis  or  meningitis.  In  all  of  these  the  number  of 
cells  would  have  given  no  indication  of  the  inflammatory  nature 
of  the  disease,  but  it  is  possible  that  the  vascular  congestion 
was  responsible  for  producing  the  very  high  percentages  of 
albumen  which  were  found.  In  one  of  these  the  fluid  was  only 
very  slightly  tinted  with  yellow,  and  gave  a  good  reduction  of 
Fehling's  solution.  In  the  other  two  the  glucose  was  diminished 
or  absent,  and  both  were  associated  with  purulent  meningitis 
above  the  level  of  the  meningeal  adhesion. 

From  the  point  of  view  of  the  cell  content,  fluids  of  this 
character  separate  themselves  into  two  classes:  (i)  those  with 
a  high  cell  content  (which  provide  the  majority  of  the  fluids 
which  coagulate  spontaneously  after  withdrawal,  i.e.  which 
contain  fibrin  ferment)  are  almost  constantly  due  to  syphilitic 
meningitis.  (2)  Fluids  with  low  (normal)  cell  content  may  be 
due  to  a  variety  of  causes,  e.g.  spinal  tumour,  arachnoid  cyst. 
Pott's  disease,  extradural  tumour  or  abscess,  chronic  basal 
meningitis,  acute  myelitis  and,  rarely,  acute  meningitis.  In 
these  the  nature  of  the  cells  (i.e.  the  presence  of  cells  other  than 
small  lymphocytes)  and  the  percentages  of  glucose  and  of 
chlorides  are  of  great  diagnostic  value. 

Pathology  of  the  syndrome. — Assuming  that  the  fluid  in  the 
lumbar  theca  is  constantly  renewed  from  above  by  being 
pumped  to  and  fro  by  the  arterial  and  venous  pulses,  then,  if 
for  any  reason  the  ventricular  fluid  fails  to  get  free  access  to 
the  lumbar  theca,  the  fluid  there  must  either  remain  stagnant 
or  be  absorbed  along  the  perineural  lymphatics  and  possibly 
also  along  the  perivascular  sheaths  of  the  spinal  veins.  In 
either  case  there  will  be  a  constant  admixture  of  lymph  by 
way  of  the  perineural  lymphatics,  the  spinal  capillaries 
and  the  Virchow-Robin  spaces  of  the  cord.  Gradually, 
therefore,  the  fluid  in  the  loculated  area  of  the  subarachnoid 
space  comes  to  correspond  more  and  more  closely  in  con- 
stitution to  blood  plasma.  In  addition,  the  albumens  may 
become  autolysed,  giving  rise  to  albumoses  and  peptones,  and  if 
any  red  blood  corpuscles  find  their  way  into  the  fluid  by  rupture 
of  congested  vessels,  these  will  be  broken  up  into  pigments 
derived  from  the  haemoglobin.  It  is  probable  also  that  venous 
congestion  below  the  level  of  the  lesion  plays,  a  considerable 


46  WASSERMANN  REACTION 

part  in  the  production  of  the  syndrome,  but  it  is  doubtful 
whether  this  is  a  constant  or  necessary  factor. 

(h)  Wassermann  reaction. — The  examination  of  the  cerebro- 
spinal fluid  as  well  as  the  blood  for  the  Wassermann  reaction 
is  of  such  importance  that  it  has  become  a  routine  measure  in 
cases  of  suspected  syphilis  of  the  nervous  system.  In  progres- 
sive general  paralysis  the  reaction  is  positive  in  both  cerebro- 
spinal fluid  and  blood  in  practically  every  case,  and  is  slightly, 
if  at  all,  influenced  by  treatment.  This  rule  also  holds  good, 
although  not  to  the  same  extent,  for  tabes  dorsalis,  but  in  this 
disease  from  20  to  30  per  cent,  of  cases  give  a  negative  reaction 
both  in  the  cerebro-spinal  fluid  and  blood.  It  may  be  assumed 
that  some  such  cases  have  become  stationary.  In  tabes  it  is 
not  uncommon  to  find  the  cerebro-spinal  fluid  giving  a  positive 
reaction  when  the  blood  gives  a  negative,  especially  in  treated 
cases.  The  reverse  condition,  a  positive  reaction  in  the  blood 
with  a  negative  reaction  in  the  fluid,  may  also  be  found  in  tabes, 
but  is  much  more  common  in  syphilitic  meningitis,  especially 
when  the  disease  is  wholly  or  chiefly  confined  to  the  vertex 
of  the  brain.  When  the  spinal  membranes  are  involved  either 
alone  or  in  conjunction  with  disease  of  the  brain,  the  Wasser- 
mann reaction  is  usually  positive  both  in  blood  and  fluid.  This 
anomaly  may  be  understood  on  the  assumption  that  the  current 
of  the  cerebro-spinal  fluid  over  the  cortex  is  towards  the 
dural  venous  sinuses,  and  that  any  antibodies  elaborated 
as  a  result  of  the  presence  of  the  Spirochaeta  pallida  in  the 
cerebral  meninges  are  rapidly  washed  out  into  the  general 
circulation.  On  the  other  hand,  a  considerable  proportion  of 
the  antibodies  formed  in  relation  to  the  membranes  covering 
the  cord  would  be  found  in  the  fluid  removed  by  lumbar  punc- 
ture. In  these  cases  of  syphilitic  meningitis  the  Wassermann 
reaction  can  be  altered  by  treatment,  and  may  be  rendered 
completely  negative  in  the  fluid  as  well  as  in  the  blood.  In  the 
meningitis  of  secondary  syphilis  the  reaction  of  the  cerebro- 
spinal fluid  is  much  less  frequently  positive  than  in  the  later 
stages,  in  spite  of  the  presence  of  large  numbers  of  lymphocytes 
and  an  increased  globulin  and  albumen  percentage. 

The  Wassermann  reactions  of  the  blood  and  cerebro-spinal 
fluid,  the  presence  of  a  lymphocytosis  of  greater  or  less  degree, 
and  a  positive  globulin  reaction  constitute  the  "  four  reactions  " 


GOLD-SOL  REACTION  47 

which  are  of  chief  value  in  the  diagnosis  of  syphiUtic  disease 
of  the  nervous  system.  By  means  of  these  reactions  it  is 
possible  to  diagnose  definitely  syphilitic  disease  of  the  nervous 
system,  but  it  is  not  always  possible  to  tell  what  form  of  disease 
is  present.  In  a  doubtful  case  the  re-examination  of  the 
cerebro-spinal  fluid  after  a  few  months  of  energetic  treatment 
will  usually  decide  whether  the  disease  is  of  the  "  parenchyma- 
tous "  or  "  interstitial  "  form.  The  effects  of  treatment  are 
usually  first  evident  in  regard  to  the  cells  and  albumen 
content.  The  disappearance  of  abnormal  cells  and  a  gradual 
diminution  of  the  lymphocytosis  are  favourable  prognostic 
signs. 

(i)  Lange's  colloidal  gold  reaction. — According  to  Cruickshank, 
the  reaction  depends  on  the  power  which  the  globulin  of  human 
serum  possesses  of  precipitating  metallic  gold  from  a  colloidal 
solution.  This  precipitation  is  checked  by  the  protective 
action  of  serum  albumen.  In  the  test  a  series  of  increasing 
dilutions  of  cerebro-spinal  fluid  from  i:  10  to  1:5120  is  added 
to  a  fixed  quantity  of  colloidal  gold,  and  the  alteration  of 
colour  is  noted  in  each  tube  in  order.  Various  curves  are  thus 
given  which  indicate  the  balance  of  the  precipitating  and 
protective  factors.  Fig.  103  indicates  the  classes  of  curve 
which  are  obtained  in  this  way. 

Experience  has  shown  that  the  results  of  the  reaction  can 
only  be  interpreted  in  relation  to  the  clinical  findings.  Thus, 
while  the  type  of  curve  indicated  for  general  paralysis  is  almost 
constantly  found  in  that  condition,  it  may  also  occur  in  acute 
forms  of  tabes  and  in  disseminated  sclerosis.  Similarly,  the 
so-called  "  syphilitic  curve  "  may  be  given  by  a  variety  of 
conditions,  among  which  may  be  mentioned  subacute  combined 
degeneration,  and  all  gradations  between  this  curve  and  that  of 
acute  meningitis  may  be  given  by  many  of  the  acute  or  chronic 
forms  of  nervous  disease,  e.g.  poliomyelitis,  lethargic  encepha- 
litis, disseminated  sclerosis,  etc.  While  it  may  be  of  some  use 
in  distinguishing  between  functional  and  organic  disease  of 
the  central  nervous  system,  the  reaction  has  probably  more 
theoretical  than  practical  value,  and  is  apt  to  lead  to  a  con- 
fusion of  diagnosis  if  too  much  reliance  is  placed  on  it. 

(/)  Relationship  of  anatomical  with  clinical  phenomena. — 
That  hydrocephalus  is  due  to  a  disorder  of  the  circulation 


48  CAUSATION  OF  HYDROCEPHALUS 

of  the  cerebro-spinal  fluid  has  long  been  known.  Theoretically 
it  may  arise  either  (i)  because  more  cerebro-spinal  fluid  is 
secreted  than  can  be  absorbed,  or  (2)  because  the  escape  of  the 
cerebro-spinal  fluid  from  the  ventricles  is  blocked.  The  former 
is  probably  the  cause  of  many  cases  of  congenital  hydrocephalus, 
and  must  be  the  cause  when  there  is  **  external  "  as  well  as 
"  internal  "  hydrocephalus;  whereas  cases  of  hydrocephalus 
following  post-basic  meningitis  or  occurring  with  tumours  in 
the  region  of  the  pons  are  to  be  explained  by  the  latter  cause. 

It  is  commonly  observed  that  a  tumour  in  one  centrum  ovale 
or  on  the  cortex  of  the  parietal  lobe  leads  to  hydrocephalus 
of  the  opposite  ventricle.  For  this  there  may  be  several 
reasons,  (i)  The  increase  in  the  size  of  one  cerebral  hemisphere 
may  compress  the  third  ventricle  laterally,  or  (2)  may  press  on 
the  roof  of  the  iter  of  Sylvius ;  (3)  the  flattening  of  the  convolu- 
tions due  to  the  increased  volumxC  of  the  brain  may  to  some 
extent  dam  back  the  cerebro-spinal  fluid  from  reaching  the 
superior  longitudinal  sinus  by  which  a  large  part  of  it  is  nor- 
mally absorbed ;  or  (4)  there  may  be  delay  in  the  escape  of  fluid 
from  the  fourth  ventricle  due  to  the  formation  of  a  "  pressure 
cone  "  consisting  of  the  amygdaloid  lobules  of  the  cerebellum, 
which  are  pressed  down  into  the  foramen  magnum  behind  the 
medulla,  taking  the  place  normally  occupied  by  the  cisterna 
magna. 

A  history  of  a  blow  on  the  head  or  a  sudden  jar  to  the  cranial 
contents,  such  as  is  caused  by  falling  in  a  sitting  position,  is 
sometimes  elicited  in  cases  of  hydrocephalus  in  the  adult. 
Trotter  has  put  forward  a  very  suggestive  theory  to  account 
for  such  cases.  By  the  jar  the  dorsal  surface  of  the  mid-brain 
is  brought  sharply  against  the  sharp  anterior  edge  of  the 
tentorium  cerebelli.  The  resulting  bruising  and  oedema  in 
this  part  of  the  brain  rapidly  closes,  temporarily  at  all  events, 
the  iter  of  Sylvius,  and  hydrocephalus  results.  Once  it  is 
present  a  vicious  circle  is  established  in  which  factors  3  and  4 
play  the  chief  part,  and  the  condition  may  remain  permanently 
or  progress  and  lead  to  the  death  of  the  patient. 


GENERAL  PATHOLOGY  49 

REFERENCES 
The  Neuron. 

BIELSCHOWSKY,     M.  I    Histologic    und    Histopathologie    des    New  en- systems. 

Berlin,  1910. 
GiERLicH,  N.,  AND  Hexheimer,  G.  :  Studien  eber  die  Neurofibrillen  im  Zentral- 

nervensystem.     Wiesbaden,  1907. 
Homen:  Changes  in  Nervous  System  after  Amputation,  Ziegler's  Beitrdge, 

vol.  vii. 
Marinesco:  La  cellule  new euse.     Paris,  1909. 
MoTT,  F.  W. :  An  Introduction  to  Neuropathology.     Allbutt  and  RoUeston's 

System  of  Medicine,  1910,  vol.  vii.,  pp.  173-236. 
Ramon-y-Cajal,  S.  :  Nouvelles  observations  sur  revolution  des  neuroblastes, 

etc.,  Anat.  Anzeigev,  Jena,  1908,  pp.  1-25  and  65-87,  also  pp.  418-448  and 

468-493  (also  previous  papers). 
Ross  Harrison  :  The  Outgrowth  of  the  Nerve  Fibre,  etc.,  and  previous  papers, 

Journal  of  Exper.  Zoology,  1910,  vol.  ix.,  p.  787. 

The  Neuroglia. 

Alzheimer,  A.:  Beitrdge  zur  pathol.  neuroglia,  etc.     Jena,  1910. 

Volland:  Zeitschrift  f.  d.  ges.  Neurologic  und  Psychiatric,  1914,  Bd.  21,  z.  194. 

Paths  of  Infection. 

Orr,  David,  and  Rows,  R.  G. :  Subacute  and  Acute  Inflammatory  Reactions 
produced  in  the  Spinal  Cord  by  Infection  of  its  Lymph  Stream,  etc., 
Brain,  191 8,  vol.  xli.,  p.  i,  and  references  to  earlier  papers. 

Teale  and  Embleton:  Studies  in  Infection — II.,  Journ.  of  Path,  and  Bad., 
1919,  vol.  xxiii.,  No.  i. 

McIntosh,  J.,  AND  FiLDES,  P.:  The  Factors  which  Govern  the  Penetration 
of  Arsenic,  etc.,  into  the  Brain,  Brain,  1916,  vol.  xxxix.,  p.  478. 

Cerebro-spinal  Fluid. 
Bruce,  A.,  and  Dawson,  J.  W.:  On  the  Relation  of  the  Lymphatics  of  the 

Spinal  Cord,  Rev.  of  N cur.  and  Psych..  1912. 
Blancheti£:re  and  Lejonne:  Gaz.  des  Hopit.,  1909,  Ixxxii.,  1303. 
Cruickshank,  J.:  The  Value  and  Mechanism   of  the  Colloidal   Gold   Test, 

Brit.  Journ.  of  Exper.  Path.,  1920,  vol.  i.,  p.  71. 
EsKUCHEN,  Karl:  Die  Lumbalpunktion.     Berlin,  1919. 
Froin:  Inflammations  meningees  avec  reactions  chromatiques,  etc.,  Gaz.  des 

Hopitaux,  Sept.,  1903. 
Head,  H.,  and  Fearnsides,  E.  G.:  Syphilis  of  the  Nervous  System,  Brain, 

1 91 5,  vol.  xxxvii. 
Hill,  Leonard  :  Physiology  and  Pathology  of  the  Cerebral  Circulation.    London, 

1896. 
Key,  G.,  and  Retzius,  A. :  Anatomic  des  Ncwensy stems  und  des  Bindesgewebcs. 

Stockholm,  1876. 
Levinson,  a.:  The  Cerebro-spinal  Fluid.     New  York,  1919. 
Majendie,  F.  :  RSchcrches  smv  Ic  Liquide  Cephalo-Rachidien.     Paris,  1825  and 

1842. 
Mestrezat,  W.  :  Lc  liquidc  cephalo-rachidien.     Paris,  191 2. 
Miller,    Brush,    Hammers   and   Felton:   Bulletin   of  the  Johns  Hopkins 

Hospital,  191 5,  vol.  xxvi.,  No.  298,  p.  391. 
MoTT,   F.   W.:    The  Oliver- Sharpey  Lectures  on  the    Cerebro-spinal  Fluid, 

Lancet,  1910,  vol.  ii. 
Quincke,  H.:  Ueber  Lumbalpunktion,  Berlin,  klin.  Woch.,  1895,  No.  41. 
Robin:  Recherches  sur  les  capillaires  de  I'encephale,  Journ.  dc  Physiologic, 

1899. 
SiCARD  AND   Descomps:    Syndrome  de  Coagulation  Massive,  etc.,  Gaz.  des 

Hopit.,  1908,  Ixxxi.,  1431. 
Weed,  L.  H.:  Studies  on  the  Cerebro-spinal  Fluid,  Journ.  Med.  Research, 

1 91 4-15,  vol.  xxxi. 

4 


CHAPTER    II 

DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

Certain  abnormalities  of  the  central  nervous  system  show 
themselves  at  birth  either  as  results  of  defective  development 
or  of  intra-uterine  disease.  These  will  be  dealt  with  under  the 
term  "  developmental  disease."  Along  with  these  must  be 
classed  injuries  received  during  birth  and  certain  cases  of 
idiocy,  in  which  the  defect  appears  to  date  from  birth,  although 
in  some  cases  it  may  be  the  result  of  a  degeneration  starting 
in  the  early  months  of  life.  Closely  related  to  the  latter  are 
those  forms  of  disease  which  tend  to  attack  several  members  of 
one  family,  and  usually  commence  about  the  same  age  in  each 
member.  These  diseases  may  start  at  any  stage  of  the  period 
of  growth,  though  many  of  them  have  a  preference  for  a  certain 
definite  age  period.  Their  tendency  to  occur  in  families 
separates  them  from  other  diseases,  and  classes  them  aetio- 
logically  as  due  either  to  an  inherited  tendency  to  degenera- 
tion or  abnormal  function  of  certain  tissues,  or  to  an  inherited 
lack  of  vitality  in  these  tissues. 

I.  Developmental  Diseases. 

(a)  Defective  development. — In  these  cases,  from  a  certain 
period  of  intra-uterine  life,  development  seems  to  have  pro- 
ceeded along  perverted  lines.  The  commonest  of  these  are 
associated  with  defective  closure  of  the  dorsal  groove  (cranio- 
rhachischisis).  The  most  complete  example  of  this  is  the 
anencephalic  monster;  less  complete  are  the  cases  of  exencephaly, 
in  which  there  is  a  larger  or  smaller  defect  in  the  cranial  vault. 
In  the  lesser  degrees  of  this  we  have  simply  a  meningocele, 
in  which  a  pouch  of  meninges,  containing  simply  fluid  or  a 
varying  amount  of  cerebral  matter,  extrudes  through  the  small 
defect  in  the  skull.     This  usually  takes  place  in  the  middle  line, 

50 


SPINA  BIFIDA  51 

and  is  most  common  either  at  the  junction  of  the  frontal  and 
nasal  bones  or  in  the  occipital  region.  When  it  affects  the 
spine  alone,  the  condition  is  termed  rhachischisis  or  spina 
bifida.  This,  again,  may  exhibit  all  degrees  from  those  in- 
compatible with  life  to  conditions  accidentally  discovered  in 
apparently  healthy  people. 

(i)  In  spina  bifida  completa  the  cord  is  exposed  in  a  greater 
or  less  extent  with  no  covering  at  all.  This  is  due  to  the 
failure  of  the  medullary  groove  to  close  in  and  form  the 
neural  canal,  and  in  consequence  the  ependyma,  which 
normally  lines  the  central  canal  of  the  cord,  here  covers  its 
dorsal  surface,  and  the  central  canal  opens  into  the  defect 
above  and  below. 

(2)  In  spina  bifida  incompleta  the  medullary  groove  is  closed, 
but  the  bony  and  connective  tissues  have  failed  to  cover  it 
normally.  There  results  an  opening  in  the  posterior  wall  of 
the  spinal  canal,  through  which  there  may  protrude  a  pouch 
of  dura  mater.  This  may  contain  simply  fluid  or  undeveloped 
medullary  substance.  Frequently  a  pad  of  fat  lies  over  the 
meningeal  pouch  or  covers  the  opening  in  the  spinal  canal 
when  no  pouch  is  protruded,  and  may  press  on  the  cord  through 
the  dura  mater.  The  term  spina  bifida  occulta  is  given  to  the 
cases  where  there  is  no  meningeal  protrusion,  and  where  the 
only  indication  of  the  abnormality  is  a  tuft  of  hairs  over- 
lying the  bony  defect.  This  defect  is  usually  in  the  lumbar 
region,  rarely  in  the  cervical  or  thoracic:  in  many  cases  the 
spinal  cord  beneath  it  is  imperfectly  developed. 

Cyclencephaly . — In  some  cases  there  is  absence  of  the  normal 
division  of  the  brain  into  two  hemispheres,  and  this  is  usually 
associated  with  the  presence  of  a  single  eye  in  the  middle  of  the 
forehead  or  of  a  double  eye  in  a  single  socket. 

Porencephaly. — Of  this  there  are  two  forms,  the  true  and  the 
false.  True  porencephaly  is  an  abnormal  development  of  the 
brain  in  which  certain  parts  of  the  cortex  of  the  brain,  both- 
white  and  grey  matter,  fail  to  be  developed,  and  in  consequence 
we  have  a  direct  communication  between  the  lateral  ventricle 
and  the  surface  of  the  brain.  Usually  this  occurs  on  the  sur-  > 
face  of  the  hemisphere,  but  a  smaller  defect  may  exceptionally 
be  found  in  the  corpus  callosum  or  the  cerebellum.  When 
it  occurs  on  both  hemispheres  the  lesions  are  symmetrical. 


52  PORENCEPHALY 

In  its  greatest  degree  the  two  hemispheres  are  almost  non- 
existent, except  for  remains  of  the  cortex  at  the  lower  part  of  the 
anterior  pole.  In  these  cases  the  lenticular  and  caudate  nuclei 
and  the  optic  thalami  persist.  The  usual  form  is  a  crateriform 
cavity  on  the  surface  of  one  or  both  hemispheres  communicating 
with  the  lateral  ventricle.  Its  sides  are  formed  by  complete 
convolutions  which  dip  down  smoothly  into  it.  These,  again, 
are  covered  by  a  vascular  membrane  continuous  with  the 
pia-arachnoid.  These  characteristics  distinguish  true  poren- 
cephaly from  pseudo-porencephaly ,  which  is  described  below 
(pp.  56  and  121). 

Another  type  of  developmental  defect  is  shown  by  those 
brains  which  present  the  features  associated  with  the  early 
months  of  foetal  existence,  and  which  do  not  show  the  division  of 
the  cranial  hemispheres  into  numerous  convolutions  {v.  Fig.  9). 

Cranio-cleido-dysostosis  is  sometimes  associated  with  defects 
of  the  central  nervous  system,  particularly  with  hydrocephalus 
and  hydromyelus. 

(b)  Other  congenital  abnormalities  are  due  to  prenatal 
diseases  or  to  degenerations  occurring  in  a  central  nervous  system 
which,  up  to  that  point,  has  been  developing  normally.  In  some 
of  these  the  disease  or  morbid  process  is  progressive;  in  others 
the  abnormality  produced  gives  rise  to  disease  in  later  life. 

One  form  of  morbid  process  which  is  often  concerned  in 
producing  such  congenital  abnormalities  has  been  termed  by 
the  French  atrophic  sclerosis.  This  may  give  rise  to  many 
forms  of  idiocy,  imbecility  and  infantile  diplegia,  and  is 
probably  at  the  bottom  of  many  cases  of  microcephaly,  as 
well  as  of  microgyria,  cerebral  asymmetry  and  external  hydro- 
cephalus. Macroscopically,  the  chief  appearance  is  that  of 
atrophy,  either  localised  or  affecting  to  a  greater  or  less  extent 
the  whole  brain  substance.  In  slight  cases  the  convolutions 
when  stripped  of  their  meninges  appear  normal,  but  examina- 
tion with  a  lens  reveals  here  and  there  depressions  or  scar-like 
puckerings.  The  surface  may  have  a  finely  worm-eaten 
appearance.  In  some  advanced  cases  the  convolutions  may  be 
irregular,  atrophied,  firmer  than  normal,  and  unlike  healthy 
brain  substance.  In  extreme  degrees  of  the  process  the  con- 
volution is  represented  by  a  thin  leaf  of  fibrous  substance,  the 
so-called    "  parchment-like    convolution."     Sections  of   such 


DEVELOPMENTAL  AND  FAMILIAL  DISEASES     53 


FiG:    9. 

Retarded  development  of  brain  from  a  diplegia  infant  eighteen  months  old. 
Primitive  convoluting  is  apparent  on  the  surface. 


54 


ATROPHIC  SCLEROSIS 


areas  show  numerous  small  cavities  in  the  grey  matter.  A 
slight  degree  of  this  process  affecting  both  hemispheres  fairly 
uniformly  may  be  one  of  the  causes  of  microcephaly.  Where 
it  affects  one  hemisphere  more  than  the  other  we  get  the  rare 


Fig.  lo. 
Cerebral  asymmetry  of  congenital  origin. 

cases  of  inequality  of  the  two  hemispheres;  in  both  cases  the 
parts  of  the  mid-  and  hind-brain  associated  with  the  sclerosed 
areas  fail  to  develop,  and  in  the  latter  case  the  cerebral 
peduncles  are  smaller  on  the  affected  side.     Where  the  disease 


DEVELOPMENTAL  AND  FAMILIAL  DISEASES     55 

is  more  localised  and  patchy  in  distribution,  one  or  more  lobes 
or  convolutions  may  be  chiefly  affected.  Microscopically  the 
condition  is  one  of  neuroglial  overgrowth  associated  with 
degeneration  of  the  neuron  substance.  The  process  appears 
to  affect  primarily  the  deeper  layers  of  the  cortex,  and  spread 


Fig.  II. 

Brain  from  case  of  diplegia  showing  shrunken  convolutions  and  patches  of 
cortical  degeneration. 

thence  to  the  underlying  white  matter  and  to  the  superficial 
layers  of  the  cortex.     The  vessels  are  affected,  showing — 
(i)  Perivascular  neuroglial  sclerosis. 

(2)  A  dilatation  of  the  adventitial  lymph  spaces  with  gran- 
ular corpuscles. 

(3)  Some  degree  of  periarteritis. 


56  HYPERTROPHIC  TUBEROUS  SCLEROSIS 

The  ependyma  is  involved,  and  may  proliferate  and  produce 
glandular  masses  which  penetrate  more  or  less  deeply  into  the 
tissue  round  the  ventricle.  This  tissue  usually  shows  a  great 
degree  of  sclerosis,  and  may  narrow  the  outlet  from  the 
ventricles,  thus  producing  internal  hydrocephalus. 

In  the  more  extreme  degrees  of  the  process  the  sclerosed 
tissue  tends  towards  cavity  formation.  This  may  happen  in 
the  following  ways : 

(i)  The  smallest  cavities  are  simply  a  dilatation  of  the 
lymphatic  sheaths  of  the  vessels. 

(2)  Others  are  areas  of  vascular  softening  which  have  become 
cystic,  as  evidenced  by  yellow  pigment  due  to  altered  blood 
either  in  the  fluid  or  in  the  walls. 

(3)  The  most  common  form  of  origin  is  the  molecular  dis- 
integration of  the  neuroglial  masses. 

Apparently  the  essential  element  in  the  disease  is  the  neurc- 
glial  overgrowth.  The  glial  cells  are  from  the  first  greatly 
multiplied,  but  giant  spider  cells  ("  fibre-forming  glial  cells  ") 
are  rare. 

Hypertrophic  tuberous  sclerosis. — In  this  disease  the  brain 
appears  sprinkled  with  whitish  nodules  of  various  sizes,  from 
that  of  a  pea  to  that  of  a  walnut.  They  may  be  rounded  or 
elongated,  and  may  occur  both  in  white  and  in  grey  matter, 
but  mainly  in  the  latter.  Cavities  may  be  formed  between 
them.  The  brain  substance  as  a  whole  shows  little  alteration, 
and  the  lesions  are  not  so  diffuse  as  in  the  atrophic  form. 
Microscopically  these  nodules  are  characterised  by  a  large 
number  of  "  fibre-forming  glial  cells."  These  are,  for  the  most 
part,  mononuclear  and  fusiform.  They  are  similar  to  cells 
seen  in  other  types  of  gliomatosis,  but  in  this  disease,  especially 
in  the  nodules  of  the  white  matter,  they  dominate  the  picture. 
The  nodule  is  mainly  composed  of  glial  fibres  with  comparatively 
few  cells.  Its  structure  blends  insensibly  with  the  surrounding 
nervous  tissue. 

Pseudo-porencephaly . — This  differs  from  the  true  form 
(p.  51,  fig.  27)  in  that  it  is  the  result  of  a  destructive  process, 
such  as  haemorrhage,  thrombosis  or  encephalitis  in  a  develop- 
ing brain.  In  this  form  the  cavity  is  lined  by  a  thin  cyst  wall, 
and  does  not  usually  communicate  with  the  lateral  ventricle. 
The  fluid  in  the  cavity  may  be  clear  or  yellowish  from  blood 


HYDROCEPHALUS 


57 


pigment.  The  cavity  cuts  across  the  convolutions  irregularly, 
and  its  walls  are  formed  of  white  matter  to  which  the  cyst  wall 
is  firmly  adherent.  Microscopically  there  is  evidence  of  the 
primary  lesion. 

Hydrocephalus. — By  external  hydrocephalus  we  mean  the 
presence  of  spaces  between  the  dura  mater  and  the  surface  of 
the  brain  filled  with  cerebro-spinal  fluid.  This  form  is  always 
congenital,  and  of  doubtful  aetiology,  but  in  some  cases  it  is 
associated  with  atrophic  sclerosis. 


Fig.  12. 
Hydromyelus  of  cervical  cord  found  in  a  child  who  died  of  acute  poliomyelitis. 


Internal  hydrocephalus  may  be  congenital  or  acquired.  In 
both  cases  it  may  be  due  to  closure  of  the  foramina  in  the 
ependymal  covering  of  the  fourth  ventricle,  or  to  other 
mechanical  blockage  of  the  outlet  of  cerebro-spinal  fluid. 

In  most  congenital  forms  it  is  due  to  stenosis  or  obstruction 
of  the  iter  of  Sylvius,  and  only  the  lateral  and  third  ventricles 
are  distended.  When  it  results  from  prenatal  inflammation 
of  the  meninges  round  the  fourth  ventricle,  or  from  closure  of 
the  foramina  of  Majendie  and  Luschka,  the  fourth  ventricle 


58  HYDROMYELUS 

may  be  very  greatly  distended,  leading  to  the  condition  called 
"hydrocele  of  the  fourth  ventricle."  The  distension  of  the 
ventricles  may  be  enormous,  and  the  brain  tissue  covering 
them  may  be  extremely  thin. 

Hydromyelus. — This  in  its  pure  form  is  a  simple  dilatation 
of  the  central  canal  of  the  cord.  The  dilatation  may  affect 
the  canal  equally  throughout  its  length  or  may  be  greater  in 
certain  areas.  It  is  probably  in  most  cases  an  error  of  develop- 
ment, but  it  may  be  associated  with  hydrocephalus.  It  may 
give  rise  to  a  progressive  symptomatology  as  the  dilated  canal 
becomes  surrounded  with  gliomatous  tissue,  and  in  this  way 
many  cases  of  syringomyelia  undoubtedly  arise.  The  two  con- 
ditions, in  fact,  insensibly  merge  into  one  another  (v.  Fig.  12) . 


2.  Birth  Injuries. 

Traumatism  during  birth  may  give  rise  to  unilateral  or 
bilateral  defects  in  the  hemispheres,  the  most  common  of  which 
are  due  to  haemorrhages  either  within  the  brain  substance  or 
upon  its  surface.  These  haemorrhages  may  be  arterial  in 
origin,  or  may  be  the  result  of  rupture  of  the  venous  sinuses, 
due  to  over-riding  of  the  cranial  bones  during  the  passage 
of  the  skull  through  the  pelvic  outlet. 

3.  Familial  and  Congenital  Diseases. 
(i.)  Cerebral  and  Myelopathic. 

(a)  Amaurotic  Family  Idiocy  {Tay-Sachs  Disease). 

Aetiology. — This  disease  was  first  observed  in  1881  by  Waren 
Tay,  who  described  fully  the  characteristic  changes  at  the 
macula.  Sachs,  in  1887,  investigated  it  from  the  neurological 
point  of  view  and  showed  its  familial  character,  as  twenty- 
eight  of  his  cases  occurred  in  fifteen  families.  Since  that  time 
a  large  number  of  cases  has  been  recorded,  all  of  which  have 
been  the  children  of  Jewish  parents.  Sachs  called  the  disease 
"  amaurotic  family  idiocy,"  but  as  the  disease  is  not  present 
at  birth,  but  develops  after  the  first  few  months,  it  is  not  pro- 
perly classed  as  "  idiocy."  The  first-born  are  rarely  affected, 
but  when  one  child  has  had  the  disease  subsequent  children 


AMAUROTIC  FAMILY  IDIOCY  59 

rarely  escape.  It  is  invariably  fatal,  usually  before  the  end 
of  the  third  year. 

Macroscopic. — The  cherry-red  spot  at  the  macula  surrounded 
by  a  pale  halo  is  clearly  seen  in  eyes  examined  post-mortem. 
The  brains  are  of  normal  development,  but  the  convolutions  are 
shrunken  and  the  sulci  widened.  There  is  an  abnormal  amount 
of  fluid  in  the  subarachnoid  space. 

Microscopic.  —  (i)  Tract  lesions.  —  The  pyramidal  tracts 
throughout  their  whole  course  are  smaller  than  normal. 
This  is  best  seen  in  the  pes  pedunculi.  But  the  tract  degenera- 
tion is  not  confined  to  the  pyramidal  system,  as  in  all  tracts  of 
the  cord  Marchi's  stain  shows  evidence  of  degeneration.  Wei- 
gert's  method  shows  signs  of  atrophy  in  the  tangential  fibres 
of  the  cortex  and  in  the  fibres  of  Gennari  in  the  visual  cortex, 
but  the  optic  radiations  and  the  medullated  fibres  of  the 
centrum  ovale  are  relatively  little  affected. 

(2)  The  chief  morbid  changes  are  seen  in  the  ganglion  cells. 
These  are  swollen,  some  globular  in  form,  others  showing 
balloon-like  swellings  at  the  base  of  the  dendrites.  The 
nucleus  usually  stains  well,  and  shows  relatively  slight  changes, 
but  is  eccentrically  placed,  being  apparently  pushed  towards 
the  apical  portion  of  the  cell  by  a  swelling  of  the  cell  sub- 
stance at  the  opposite  pole.  It  is  surrounded  by  a  zone  of 
granular  matter  which  takes  the  stain  by  Nissl's  method, 
although  healthy  Nissl  granules  are  rarely  seen.  Elsewhere 
the  cell  protoplasm  is  clear  and  stains  poorly,  so  that  it  is  diffi- 
cult to  distinguish  the  cell  margin  from  the  surrounding  tissues, 
and  vacuoles  of  varying  size  may  be  present.  The  swelling 
may  be  very  great  and  the  pyramidal  cells  may  measure 
from  30  [jl  to  60  jj,.  A  balloon-like  swelling  on  the  proximal 
portion  of  one  of  the  dendrites,  separated  from  the  cell  by  a 
narrow  neck,  is  sometimes  seen,  or  there  may  be  varicose 
swellings  in  the  dendrites  a  short  distance  from  the  cell  body. 
By  Bielschowsky's  neuro-fibrillar  stain  it  is  evident  that  the 
fibrils  in  the  dendrites  are  relatively  little  affected.  They  do 
not,  however,  run  through  the  cell  body  in  a  normal  manner, 
but  are  pushed  aside  by  the  globular  swelling  or  vacuolation, 
and  are  often  seen  lying  bunched  closely  together  at  the  side  of 
the  cell.  In  a  similar  manner  they  run  round  and  not  through 
the  swellings  in  the  dendrites. 


6o      DEVELOPMENTAL  AND  FAMILIAL  DISEASES 


r           

-■"'f^-p'^rrmfk 

JillilSfiisH*^ 

V, 
-        \i 

# 

:~  %. 

■   m 

'    '  \        1 

b 
Fig.  13. 

a,  Cells  from  dorsal  horn  and  Clarke's  column  in  a  case  of  amauroHc  family 
idiocy. 

b,  Purkinje  cells  from  the  same  case. 


AMAUROTIC  FAMILY  IDIOCY  6i 

Mott  has  shown  that  these  degenerated  nerve  cells  contain 
an  abnormally  large  amount  of  lipochrome  granules  which  stain 
by  Scharlach  R.  or  Sudan  III,  and  also  by  Marchi's  method. 
The  ganglion  cells  are  surrounded  by  "  parasitic  "  glia  cells,  in 
which  the  lipochrome  granules  are  rather  larger,  and  granular 
corpuscles  filled  with  fatty  substances  are  numerous.  These 
changes  in  the  nerve  cells  are  seen  throughout  the  central 
nervous  system.  They  are,  perhaps,  most  marked  in  the  cells 
of  the  hippocampal  region  and  frontal  lobes,  but  are  present  in 
the  pyramidal  cells,  and  in  the  cells  of  the  ventral  horns  and 
Clarke's  column.  The  cerebellum  is  less  affected,  but  certain 
of  the  cells  of  Purkinje  show  similar  changes.  Neuroglial 
overgrowth  is  slight,  and  seems  to  be  secondary  to  the  degenera- 
tion of  neurons.  Apart  from  some  degree  of  congestion  the 
blood  vessels  are  normal. 

The  changes  in  the  retina  are  essentially  of  the  same  nature. 
The  ganglion  cells  show  lipochrome  granules,  but  there  is  little 
change  in  the  nerve  fibrils.  The  fovea  centralis  is  abnormally 
thin,  and  is  surrounded  by  a  zone  of  slight  oedema.  The  optic 
nerves  show  some  degree  of  atrophy,  and  this  is  also  seen  in  the 
optic  tracts. 

From  the  microscopic  appearances  it  seems  that  the  "  hyalo- 
plasm "  of  the  nerve  cells  is  primarily  affected,  becoming 
swollen,  and  undergoing  degeneration  into  various  lipoid 
substances.  The  changes  in  the  Nissl  granules  follow  rapidly, 
but  the  neuro-fibrils  continue  for  some  time  comparatively 
immune.  The  cells  may  die  or  may  enter  a  state  of 
necrobiosis  in  which  they  continue  until  the  death  of  the 
patient. 

From  the  pathological  standpoint  this  disease  is  scarcely 
distinguishable  from  certain  cases  oi  familial  cerebral  degenera- 
tion with  macular  changes  occurring  at  a  later  period  of  child- 
hood, and  not  confined  to  the  Jewish  race.  Although  the 
clinical  picture  varies  in  some  ways,  and  the  typical  macular 
changes  of  Tay-Sachs  disease  are  not  present,  the  classical 
description  of  the  pathological  findings,  both  macroscopic 
and  microscopic,  applies  with  few  differences  to  the  two  forms. 


62  WERDNIG-HOFFMANN  PARALYSIS 

{b)  Progressive  Spinal  Muscular  Atrophy  of  Infants 
(Werdnig- Hoffmann  Paralysis). 

This  rare  disease  was  described  first  by  Werdnig  in  189 1  and 
by  Hoffmann  in  1894.  The  total  number  of  recorded  cases  is 
still  small  (between  twenty  and  thirty),  but  sufficient  have  been 
examined  to  establish  the  specificity  of  the  disease  and  the 
nature  of  the  pathological  changes  special  to  it. 

Aetiology. — The  patients  are  usually  well  developed  at  birth 
and  appear  normal,  but  after  a  few  weeks  or  months  muscular 
weakness  sets  in,  commencing  in  the  muscles  of  the  back  and 
the  proximal  parts  of  the  limbs,  and  spreading  to  the  inter- 
costal and  abdominal  muscles,  the  neck  muscles  and  the  muscles 
controlling  the  knee  and  elbow.  The  diaphragm  and  the 
muscles  supplied  by  the  cranial  nerves  are  spared,  and  the 
movements  of  the  fingers  and  toes  are  usually  affected  late 
in  the  disease.  The  paralysis  steadily  increases  and  leads 
to  the  death  of  the  patients  at  ages  varying  from  a  few  months 
to  six  years.  In  several  instances  more  than  one  member  of  a 
family  has  been  affected,  but  in  no  case  has  any  evidence  of 
hereditary  transmission  been  recorded;  nor  does  the  disease 
affect  particularly  the  last  members  of  families. 

From  the  point  of  view  of  pathology  it  is  related  most  closely 
to  the  classical  types  of  progressive  muscular  atrophy  (motor 
neuron  disease,  p.  271),  but  has  an  inverse  distribution  of  the 
paralysis.  In  both  cases  we  are  absolutely  in  the  dark  as  to 
the  cause  of  the  disease. 

Histology. — The  chief  changes  are  those  found  in  the  ventral 
horn  cells  and  their  nerve  roots.  These  cells  are  greatly 
diminished  in  number,  especially  in  the  older  and  more  advanced 
cases,  and  some  of  them  show  chromolysis  of  varying  severity. 
In  some  cases  very  little  chromolysis  has  been  present,  but  the 
cells  are  definitely  smaller,  and  much  less  numerous  than  normal. 
The  ventral  nerve  roots  are  thin  and  their  myelin  stains 
poorly  as  compared  with  the  dorsal  nerve  roots.  Marchi's 
method  shows  recent  myelin  degeneration  in  some  cases. 
T-he  affected  muscles  also  show  definite  changes,  which  appear 
to  be  secondary  to  the  atrophy  of  the  neurons.  A  varying 
proportion  of  the  muscle  fibres  are  of  normal  size  or  slightly 
larger,  and  either  retain  their  usual  polygonal  outline  or  appear 


FRIEDREIGH'S  ATAXIA  63 

rounded  on  section,  some  of  them  showing  hyaUne  changes. 
Their  nuclei  are  not  increased  in  number,  and  are  present  only 
in  relation  to  the  sarcolemma.  On  the  other  hand,  a  large 
number  of  the  muscle  fibres  are  extremely  small,  measuring 
10  fjL  or  less  in  diameter.  Sometimes  it  is  possible  to  see 
a  large  fibre  breaking  up  into  a  number  of  smaller  fibres. 
The  nuclei  of  the  small  fibres  appear  greatly  increased,  but  both 
large  and  small  fibres  usually  preserve  their  transverse  striation. 
Marchi's  method  shows  evidence  of  fatty  degeneration  in  diffuse 
stippling  of  the  muscle  fibres  with  black  dots. 

The  intermuscular  fibrous  tissue  is  increased  and  numerous 
fat  cells  are  present  between  the  fibres,  but  these  changes  do  not 
approach  the  degree  seen  in  myopathic  muscles.  The  appear- 
ances, on  the  whole,  resemble  those  seen  in  the  wasting  of 
muscles  following  disease  of  their  motor  nerves,  although  certain 
features  of  this  are  wanting.  This  may,  perhaps,  be  explained 
by  the  age  of  the  patient  and  the  relatively  undeveloped  state 
of  the  muscles  when  they  become  affected. 

(c)  Friedreich' s  Disease. 

Aetiology. — The  disease  tends  to  attack  more  than  one  member 
of  the  same  family,  but  it  is  not  often  directly  inherited,  and 
cases  with  regard  to  which  no  family  history  can  be  obtained 
are  by  no  means  uncommon.  It  affects  both  sexes,  and  its 
onset  is  generally  noticed  either  in  childhood  or  in  early  adoles- 
cence. The  occurrence  of  the  disease  in  several  members  of 
the  same  family,  and  the  fact  that  some  portions  of  the  central 
nervous  system  have  often  been  found  to  be  unusually  small, 
lead  to  the  conclusion  that  the  disease  is  really  due  to  some 
inherent  congenital  defect.  It  may  be  cited  as  a  good  example 
of  a  nervous  abiotrophy,  or  in  other  words  of  a  tendency  to 
early  decay  and  subsequent  death  of  certain  tracts  in  the 
central  nervous  system  for  no  apparent  reason  other  than 
their  lack  of  vitality. 

Morbid  anatomy. — Gross  examination  of  the  central  nervous 
system  often  reveals  a  fairly  well-developed  brain  with  a  some- 
what abnormally  slender  spinal  cord.  In  only  a  few  instances 
has  the  cerebellum  been  small  in  proportion  to  the  cerebrum 
or  shown  any  naked-eye  changes. 


64     DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

On  cross  section  through  the  spinal  cord  sclerosis  of  the 
dorsal  and  lateral  columns  is  readily  distinguished,  and  the 
definite  limitations  of  the  sclerotic  process  can  be  best  studied 
by  the  Weigert-Pal  method.  Such  sections  show  that  a  primary 
degeneration  of  the  dorsal  columns,  of  the  pyramidal  and  of 
the  spino-cerebellar  tracts  is  the  essential  feature  of  the 
disease.  If  the  dorsal  columns  are  examined  more  minutely 
it  will  be  seen  that  the  endogenous  fibres  suffer  less  than  those 
which  enter  the  spinal  cord  through  the  dorsal  roots.  Goll's 
column  is  generally  more  completely  degenerated  than  that 
of  Burdach.  Apparently  all  the  dorsal  root  fibres  suffer  to 
some  extent,  as  there  is  degeneration  not  only  of  those  which 
ascend  in  the  dorsal  columns,  but  also  of  those  which  pass 
into  the  central  grey  matter  to  end  either  in  the  region  of  Clarke's 
column  or  in  the  ventral  horns.  The  degeneration  in  all  the 
dorsal  root  fibres  becomes  less  marked  as  we  pass  from  the 
spinal  cord  towards  the  dorsal  root  ganglia.  These  ganglia 
themselves  are  usually  healthy  or  show  slight  cellular  changes 
which  are  probably  secondary  to  the  degeneration  in  the  axis 
cylinder  process.  In  the  lateral  columns  is  found  symmetrical 
degeneration  of  the  pyramidal  tracts  throughout  their  length, 
the  area  of  sclerosis  being  better  marked  in  sections  taken  from 
lower  levels.  The  direct  cerebellar  tract  is  also  constantly 
degenerated  and  certainly  more  often  affected  than  Gowers' 
tract,  which  sometimes  escapes  in  cases  which  have  not 
survived  very  long.  Atrophic  changes  are  well  marked  in  the 
cells  of  Clarke's  column,  and  the  latter  are  often  much  reduced 
in  number. 

Along  with  the  degeneration  of  the  various  tracts  there  is 
the  usual  overgrowth  of  glial  tissue,  which  must  be  regarded  as 
a  secondary  phenomenon  in  spite  of  the  fact  that  its  excessive 
proliferation  and  curious  irregular  arrangement  in  so-called 
whorls  at  one  time  led  to  the  belief  that  it  was  the  essential 
pathological  factor  in  the  disease. 

Microscopical  examination  of  the  brain  shows  that  the  Betz 
cells  of  the  Rolandic  area  undergo  atrophy  and  some  diminution 
in  number,  which  is  exactly  what  one  would  expect,  considering 
the  degeneration  of  the  pyramidal  fibres.  In  the  cerebellum 
microscopical  changes  are  by  no  means  constant,  and  cannot 
be  considered  typical  of  Friedreich's  disease.     The  peripheral 


FRIEDREICH'S  ATAXIA 


65 


Fig.  14. 

Three  sections  from  a  case  of  Friedreich's  ataxy  stained  by  the 
Weigert-Pal  method. 


66.    DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

nerves  have  sometimes  been  reported  to  be  healthy,  but  in 
other  cases  have  shown  degenerative  changes. 

If  the  Marchi  method  is  used  for  the  examination  of  sections, 
the  degeneration  can  be  traced  in  the  nerve  fibres  considerably 
nearer  to  their  cells  of  origin.  For  instance,  degeneration  can 
be  traced  in  the  pyramidal  fibres  much  higher  in  the  brain- 
stem and  mid-brain  than  is  shown  in  the  Weigert-Pal  sections. 
There  is  abundant  evidence  to  show  that  the  neuronic  decay 
is  more  marked  the  greater  the  distance  from  the  ganglion  cell. 
On  the  other  hand,  the  Marchi  stain  is  not  adapted  to  the  display 
of  all  degenerated  fibres  because  only  those  which  have  recently 
succumbed  are  brought  into  prominence  by  this  method. 

The  relationship  of  anatomical  to  clinical  phenomena. — The 
symptoms  and  physical  signs  in  Friedreich's  disease  can  be 
closely  correlated  with  the  anatomical  findings.  The  marked 
ataxy  is  the  result  of  degeneration  in  the  dorsal  columns 
and  in  the  cerebellar  tracts.  The  weakness  of  the  limbs  and 
the  trunk  muscles,  the  absence  of  the  abdominal  reflexes,  and 
the  presence  of  extensor  responses,  are  to  be  associated  with  the 
degeneration  of  the  pyramidal  tracts.  The  absence  of  tendon 
jerks  is  the  result  of  decay  in  those  fibres  of  the  dorsal  roots 
which  form  the  afferent  part  of  the  reflex  arc,  upon  which  the 
maintenance  of  those  jerks  depends.  The  nystagmus  is  not 
quite  so  easily  explained,  as  the  mechanism  of  that  physical 
sign  is  not  yet  fully  understood.  At  the  same  time,  we  recog- 
nise that  nystagmus  is  a  common  sign  of  disease  of  the  cerebellar 
system.  The  marked  scoliosis  in  this  disease  is  probably  de- 
pendent upon  a  certain  amount  of  asymmetry  in  the  progressive 
loss  of  power  in  the  trunk  muscles  and  on  a  loss  of  tone  in  the 
spinal  muscles  during  the  period  of  skeletal  growth,  as  evi- 
denced by  its  frequency  in  juvenile  tabes.  The  pes  cavus  is 
probably  associated  with  degeneration  of  the  pyramidal 
tracts,  as  it  is  also  found  in  many  cases  of  early  amyotrophic 
lateral  sclerosis. 

{d)  Progressive  Lenticular  Degeneration. 

This  rare  and  interesting  disease  has  recently  been  thoroughly 
investigated  by  Kinnier  Wilson,  who  has  analysed  all  the  cases 
published  up  till  1910,  and  has  collected,  with  his  own  cases, 
twelve  instances  of  the  disease.     Its  characteristics,  from  the 


PROGRESSIVE  LENTICULAR  DEGENERATION    67 

pathological  standpoint,  are  its  familial  incidence  and  the 
constancy  of  coarse  cirrhosis  of  the  liver  with  degeneration  of 
the  lenticular  nuclei.  Of  his  collected  cases,  three  occurred 
in  one  family,  three  in  a  second,  two  in  a  third,  and  four 
occurred  sporadically. 

Aetiology. — The  age  of  commencement  of  the  disease  varied 
from  ten  years  in  the  youngest  to  twenty-six  in  the  oldest, 
the  average  being  fifteen.  It  is  thus  a  disease  of  adolescence. 
It  attacks  either  sex  indiscriminately,  and  may  run  its  fatal 
course  in  any  period  from  four  months  to  seven  years.  In 
some  cases  there  had  been  an  attack  of  jaundice  before  the 
onset  of  the  disease,  but  otherwise  no  predisposing  causes  were 
found.  Neither  alcohol  nor  syphilis  plays  any  role  in  its 
aetiology. 

Macroscopic  appearances. — The  only  changes  in  the  nervous 
system  were  those  of  primary  symmetrical  degeneration  of 
the  lenticular  nucleus  and  secondary  degeneration  in  the  tracts 
passing  from  it.  The  degeneration  chiefly  affects  the  put  amen, 
to  a  less  extent  the  globus  pallidus.  The  caudate  nucleus 
and  the  internal  capsule  may  be  more  slightly  affected. 
All  stages,  from  a  spongy  worm-eaten  appearance,  with  some 
discoloration  of  the  nucleus,  to  complete  cavitation  are  found. 

Microscopically,  the  chief  change  is  an  overgrowth  of  neuro- 
glia with  a  multiplication  of  neuroglia  cells  which  may  be 
extremely  numerous.  This  overgrowth  of  glia  tissue  goes  on 
to  disintegration  and  cavity  formation,  the  nerve  cells  and 
fibres  and  the  blood  vessels  being  affected  by  the  gliosis. 
The  few  remaining  nerve  cells  are  atrophic  and  stain 
deeply;  the  myelin  sheaths  are  broken  up,  and  numerous 
granular  corpuscles  scattered  through  the  degenerated  area 
are  full  of  fatty  globules.  The  vessels  share  passively  in  the 
process  of  disintegration,  being  broken  up  and  disappearing; 
in  the  cases  which  Wilson  examined  personally,  he  found  no 
evidence  of  endarteritis  or  thrombosis,  the  only  changes  being 
hyaline  degeneration  of  the  middle  coat,  dilatation  of  the 
adventitial  lymphatics,  and  sometimes  perivascular  gliosis. 
He  concludes  that  blockage  of  the  arteries  plays  no  part  in 
the  aetiology  of  the  disease.  The  nerve  cells  of  the  cortex, 
cranial  motor  nuclei  and  anterior  horns  were  found  to  have 
undergone   only    the    changes    due    to    prolonged    muscular 


68     DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

inactivity,  some  of  them  undergoing  pigmentary  degeneration 
and  early  chromolysis,  and  others  staining  more  darkly  than 
normal.  Sometimes  they  showed  evidence  of  reaction  to  a 
terminal  toxaemia. 

The  changes  in  the  liver  were  those  of  cirrhosis,  similar 
to  the  "  hob-nailed "  form,  but  even  coarser.  The  pro- 
jections on  the  surface  are  described  as  varying  in  size  from  a 
threepenny-bit  to  a  shilling  in  some  cases,  and  as  rather  smaller 
in  others.  The  amount  of  fibrous  tissue  in  the  portal  tracts 
may  be  as  great  as  is  ever  se-en  in  cirrhosis ;  and  there  was  evi- 
dence of  proliferation  of  the  liver  cells  and  formation  of  new 
bile  ducts  in  the  cirrhotic  tissue.  The  whole  organ  was  yellow- 
ish in  colour  and  usually  somewhat  diminished  in  size,  but  no 
ascites  was  found  in  any  case.  The  spleen  was  usually  firmer 
than  normal,  and  sometimes  enlarged.  This  may  have  been 
secondary  to  the  disease  of  the  liver. 

Wilson  considers  it  probable  that  the  changes  in  the  brain 
are  due  to  the  selective  action  of  a  toxin  formed  in  the  liver  or 
associated  with  the  hepatic  disease,  the  cirrhosis  thus  being  the 
primary  affection  and  the  lenticular  degeneration  secondary. 
He  notes  that  there  is  a  familial  form  of  "  icterus  neonatorum  " 
in  which  yellow  pigment  is  found  to  stain  the  lenticular  nucleus 
and  corpus  Luysii  deeply,  the  dentate  and  olivary  nuclei  and 
the  sensory  nuclei  of  the  medulla  and  pons  less  intensely,  and 
the  cortex  cerebri,  caudate  nuclei  and  optic  thalami  faintly, 
if  at  all.  In  these  cases  the  pigment  is  found  in  the  bodies  of 
the  nerve  cells.  It  is  well  known  that  in  other  forms  of  jaundice 
the  nervous  system  shows  little  or  no  pigmentation  and  that 
there  is  no  evidence  of  selective  action  when  staining  does 
occur. 

(e)  Huntington's  Chorea. 

Aetiology. — Little  is  known  about  the  true  cause  of  this  rare 
disease,  which  is  characterised  by  its  hereditary  tendencies 
and  the  onset  of  symptoms  in  the  middle  period  of  life.  Several 
members  of  a  family  may  be  affected,  and  direct  transmission 
from  parent  to  child  is  by  no  means  uncommon.  The  disease 
may  be  inherited  through  either  parent,  and  if  a  child  escapes 
the  next  generation  will  probably  remain  unaffected.  The  two 
sexes  are  equally  liable  to  inherit  the  disease.      Sporadic  cases 


HUNTINGDON'S  CHOREA  69 

are  not  very  uncommon.  A  great  many  theories  have  been 
advanced  to  account  for  the  pathological  process  at  work,  but 
few  have  any  substantial  foundation.  As  it  is  evident  that  the 
morbid  influence  at  work  must  be  of  prenatal  origin,  some 
observers  have  assumed  that  the  victims  of  the  disease  are  born 
with  hereditary  malformations  either  in  the  nerve  cells,  the 
neuroglia,  or  the  interstitial  tissues  of  the  cerebral  hemi- 
spheres. On  this  malformation  may  be  grafted  the  gross 
changes  which  are  usually  observed  in  fatal  cases. 

Morbid  anatomy. — The  gross  changes  found  in  the  brain 
are  variable  and  include  pachymeningitis,  simple  or  haemor- 
rhagic,  chronic  leptomeningitis  with  adhesion  of  the  meninges 
to  the  cortex,  atrophy  of  the  convolutions  with  a  compensatory 
deepening  of  the  sulci  and  increase  of  the  cerebro-spinal  fluid. 
Under  the  microscope  there  is  always  found  some  increase  of 
the  neuroglia  and  degeneration  of  nerve  cells.  Small  areas 
of  softening  and  disseminated  foci  of  encephalitis  are  also 
described.  Special  importance  has  been  attached  to  the 
atrophy  of  the  cells  between  the  first  and  second  cortical 
layers.  On  the  other  hand,  some  authors  consider  that  vascular 
changes  are  of  primary  significance  and  that  the  disease  of 
the  blood  vessels  results  in  neuroglial  proliferation  and  other 
tissue  changes. 

Perhaps  the  most  constant  changes  and  those  which  many 
pathologists  consider  to  be  primary  are  the  degeneration  of 
pyramidal  cells,  most  marked  in  the  psycho-motor  areas,  and 
of  the  smaller  ganglion  cells  of  the  corpus  striatum,  especially 
in  the  putamen  and  caudate  nucleus.  There  is  corresponding 
degeneration  of  the  pyramidal  tracts  and  glial  increase  in  the 
areas  affected. 

It  is  possible  that  the  variety  of  morbid  changes  described 
is  partly  due  to  the  confusion  between  true  hereditary  chorea 
and  cases  of  senile  dementia  associated  with  choreiform  move- 
ments, in  which  vascular  and  meningeal  disease  would  readily 
account  for  the  clinical  symptoms. 

Relationship  of  anatomical  to  clinical  phenomena. — It  is  not 
very  difficult  to  correlate  the  degenerative  and  other  changes 
in  the  psycho-motor  cortex  with  the  progressive  dementia 
which  forms  one  of  the  chief  features  of  the  disease.  On  the 
other  hand,  the  pathological  basis  of  choreiform  movements 


70     DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

is  a  subject  concerning  which  there  has  been  much  discussion, 
and  the  changes  found  both  in  this  disease  and  in  Sydenham's 
chorea  do  not  afford  sufficient  grounds  for  the  solution  of  this 
problem. 

(ii.)  Neural. 

(/)  Peroneal  Atrophy  (Char cot-Marie-Tooth  Paralysis). 

History  and  aetiology. — This  disease  was  first  described  by 
Charcot  and  Pierre  Marie  in  1886,  and  by  Tooth  independently 
in  the  same  year.  Two  years  later  Herringham  had  collected 
a  pedigree  comprising  twenty  cases  in  five  generations.  In 
this  family  the  transmission  resembled  that  of  haemophilia,  in 
that  only  males  were  affected,  and  the  disease  was  transmitted 
by  the  females.  But  in  other  families  both  sexes  are  affected, 
and  the  disease  is  transmitted  by  either  parent.  As  a  rule,  males 
are  much  more  frequent  sufferers  than  females. 

It  is  essentially  a  hereditary  familial  disease,  and  usually 
starts  in  the  first  decade,  but  the  onset  may  be  delayed  till 
the  second  or  third  decade.  Its  course  is  very  slow  and,  as 
the  paralysis  remains  limited  to  certain  muscles,  life  is  not 
endangered.  Consequently  pathological  material  has  been 
very  scanty,  and  there  is  no  unanimity  of  opinion  as  to  the 
essential  pathological  process.  It  is  undoubtedly  a  disease 
su'  generis,  and  has  no  relation  to  the  myopathies. 
.  The  muscles  affected  are,  first,  those  supplied  by  the  peroneal 
nerves,  especially  the  peroneal  group;  later  the  calf  muscles 
and  the  small  muscles  of  the  hands.  In  some  reported  cases 
the  disease  has  been  first  noticed  in  the  hands.  Atrophy  does 
not  spread  to  other  muscles,  except  in  a  limited  degree  to 
the  thighs  and  forearms.  There  is  always  club-foot  of  the  pes 
equinus  or  equinovarus  type,  and  the  claw  hand  typical  of 
Aran-Duchenne  paralysis.  Except  for  these  there  is  no  de- 
formity. Fibrillary  tremor  in  the  muscles  resembling  that 
seen  in  motor  neuron  disease  and  some  sensory  disturbances, 
are  often  present. 

Histology. — The  nervous  system  is  affected  both  on  its  motor 
and  sensory  side.  Degeneration  of  the  dorsal  columns,  especi- 
ally in  the  tract  of  Goll,  advances  pari  passu  with  atrophy 
of  the  ventral  horn  cells.  The  spinal  ganglion  cells  and  the 
cells  of  Clarke's  column  also  show  atrophic  changes.     Later 


PERONEAL  ATROPHY 


71 


the  pyramidal  tracts  may  become  degenerated.  On  the  other 
hand,  in  certain  cases  no  demonstrable  lesion  of  the  spinal  cord 
has  been  found.  The  ventral  nerve  roots  are  usually  atrophied, 
and  there  is  some  degree  of  interstitial  neuritis  in  the  branches 
of  the  peroneal  nerves.  This  appears  to  be  the  most  constant 
and,  probably,  the   primary  morbid  process  of   the  disease. 


Fig.  15. 

Section  of  muscle  from  a  case  of  peroneal  atrophy. 

The  change  in  the  muscles  is  similar  to  that  seen  in  lesions  of 
the  motor  nerves.  It  is  essentially  secondary  to  the  changes  in 
the  nerves  and  spinal  cord. 


(g)  Progressive  Hypertrophic  Interstitial  Neuritis  of 
Children. 

This  disease  was  described  in  1893  by  Dejerine  and  Sottas 
as  occurring  in  a  brother  and  sister,  and  the  details  of  the 
pathological  examination  of  one  case  were  given.  Since  then 
a  small  number  of  cases  have  been  observed  in  which  the  same 
clinical  and  pathological  features  were  present.  Some  of  these 
have  been  isolated  cases,  in  others  another  member  of  the 


72        PROGRESSIVE  HYPERTROPHIC  NEURITIS 

family  has  been  affected,  but  there  has  been  no  evidence  of 
hereditary  transmission. 

The  disease  usually  commences  in  the  first  decade,  sometimes 
in  the  second.  It  is  characterised  (i)  by  muscular  wasting, 
starting  in  the  muscles  of  the  leg  and  spreading  to  those  of  the 
hands  and  the  mouth,  and  later  affecting  the  limbs  more 
generally;  (2)  by  sensory  disorders  of  the  polyneuritic  type, 
along  with  inco-ordination  in  both  upper  and  lower  limbs; 
(3)  by  Argyll-Robertson  pupil,  mypsis  and  nystagmus;  (4)  by 
kyphoscoliosis  and  talipes  equinovarus;  and  (5)  by  thickening 
of  all  the  peripheral  nerves,  which  can  be  felt  and  sometimes 
seen  as  firm  cords  under  the  skin.  This  last  feature  is  most 
characteristic  of  the  disease,  but  the  clinical  picture  is  other- 
wise quite  constant.  In  spite  of  the  Argyll-Robertson  pupil, 
syphilis  appears  to  play  no  part  in  the  aetiology. 

Morbid  anatomy  and  histology. — The  swelling  of  the  nerves  is 
diffuse  and  uniform,  the  consistency  being  firmer  in  Iheir 
peripheral  parts.  Both  ventral  and  dorsal  spinal  nerve 
roots  are  usually  thickened,  but  in  some  cases  only  the 
dorsal  roots  are  affected. 

Histologically,  there  is  found  a  diffuse  interstitial  neuritis 
which  in  the  more  peripheral  parts  is  characterised  by 
dense  fibrous  tissue  surrounding  the  individual  nerve  fibres. 
Nearer  to  the  central  nervous  system  and  especially  in  the  spinal 
nerve  roots  the  interstitial  tissue  is  more  cellular,  sometimes 
myxomatous,  but  otherwise  presents  the  same  arrangement. 
In  the  peripheral  parts  of  the  nerves  both  axon  and  myelin 
sheath  have  usually  disappeared  completely,  but  closer  to  the 
cord  there  may  be  some  irregular  remnants  of  myelin  sheaths 
and  degenerated  axons,  and  it  may  be  possible  to  observe 
skeins  of  new  fibrils  running  out  in  the  old  nerve  tubes.  There 
is  great  increase  of  the  cells  of  the  sheath  of  Schwann  and  those 
of  the  interfibrillar  connective  tissue.  Changes  are  also  found 
in  the  spinal  cord,  especially  degeneration  of  the  dorsal 
columns  affecting  the  dorsal  root  zones  and  the  columns  of 
Goll  and  Burdach.  The  cells  of  the  spinal  ganglia  and  of 
the  ventral  cornua  appear  normal. 


FAMILY  PERIODIC  PARALYSIS  73 

(iii.)  Myopathic. 

(h)  Family  Periodic  Paralysis. 

Aetiology. — The  famUial  character  is  well  established,  and  the 
disease  seems  to  fall  with  equal  frequency  on  the  two  sexes.  The 
disease  may  be  transmitted  either  through  the  father  or  the 
mother.  In  some  cases  it  is  associated  with  migraine  either 
in  the  patient  himself  or  in  other  members  of  the  family.  Its 
onset  is  not  usually  observed  until  after  the  age  of  six,  but 
in  certain  cases  the  attacks  undoubtedly  have  been  present 
from  infancy.  They  are  very  irregular,  and  true  periodicity 
is  seldom  observed.  They  come  on  either  during  a  period  of 
rest  after  severe  exercise  or  during  a  prolonged  period  of 
rest.  In  some  cases  they  appear  to  have  some  relation  to 
errors  in  diet. 

The  paralysis  affects  chiefly  the  proximal  muscles,  especially 
in  the  lower  limbs.  The  peripheral  parts  of  the  limb  are 
affected  along  with  the  trunk  in  more  severe  attacks,  and  the 
muscles  of  the  neck  are  sometimes  paralysed.  Usually  the 
cranial  nerves  escape,  but  ptosis  of  the  upper  eyelid  is  not 
very  infrequent.  Although  the  intercostals  may  be  paralysed, 
the  diaphragm  seems  to  escape,  but  several  cases  have  been 
reported  where  the  patient  died  during  an  attack,  presumably 
from  respiratory  failure. 

During  attacks  the  muscular  response  diminishes  progres- 
sively and  equally  to  the  various  forms  of  stimulation,  e.g. 
volitional,  reflex,  galvanic,  faradic,  mechanical.  During  the 
paralysis  there  is  neither  spasticity  nor  loss  of  tone,  and  there 
are  no  sensory  changes.  The  attacks  pass  off,  leaving  no  im- 
pairment of  muscular  power,  but  when  they  continue  for  long 
periods  some  contracture  may  result. 

Certain  observations  have  been  put  forward  to  account  for 
the  disease.  Goldflam  found  that  the  urine  of  patients  just 
before  and  during  an  attack  had  toxic  properties,  but  this  has 
not  been  confirmed  by  other  observers.  Others  have  found 
that  the  occurrence  of  vomiting  in  the  early  stages  of  the  attack 
has  caused  the  paralysis  to  pass  off  rapidly.  Again,  by  careful 
dieting,  and  avoiding  special  articles  of  food,  such  as  pork, 
cheese,  beer,  etc.,  some  sufferers  from  this  disease  have  been 
able  to  take  violent  exercise  without  an  attack  occurring. 


74  MYOTONIA 

During  an  attack  arterial  tension  is  usually  raised,  and  there 
may  be  an  increase  in  the  cardiac  dulness. 

The  absence  of  electrical  response  during  the  attacks  indi- 
cates that  the  seat  of  the  paralysis  lies  in  the  muscles  them- 
selves. The  nature  of  this  paralysis  is  uncertain,  but  from  the 
histological  appearances  of  muscles  excised  during  an  attack, 
and  from  other  facts  already  mentioned,  it  seems  probable 
that  it  is  associated  with  lymph  stasis,  oedema  and  the 
accumulation  of  toxic  products  in  and  around  the  muscle 
fibres. 

(i)  Myotonia  {Thomsen's  Disease). 

Aetiology. — Nothing  is  known  of  the  aetiology  of  this  disease 
except  the  well-established  facts  of  its  familial  character,  its 
appearance  in  the  earliest  years  of  life  suggesting  that  it  is  really 
congenital,  and  its  tendency  to  affect  the  males  of  the  family 
more  than  the  females. 

Anatomy. — The  general  musculature  is  usually  well  developed 
and  sometimes  gives  the  appearance  of  hypertrophy.  Macro- 
scopically,  the  muscles  have  perhaps  a  paler  and  clearer 
appearance  than  normal,  but  are  not  fatty. 

Microscopically,  in  pieces  removed  during  life  there  is  a  very 
definite  enlargement  of  the  muscular  fibres,  which  average  from 
50^  to  100  jLi  (normal  12  jut  to  yo  ju).  The  fibres  are  rounder 
than  normal,  the  transverse  striations  are  poorly  marked  and 
the  sarcolemma  nuclei  are  increased  in  number.  In  muscles 
examined  after  death  various  other  changes  have  been  described 
which  may  be  due  to  other  influences,  but  when  removed  during 
life  the  above  appearances  are  constant.  No  constant  changes 
have  been  found  in  the  nerves  or  spinal  cord,  which  are  usually 
healthy. 

Physico-pathology . — Much  work  has  been  done  on  the  reac- 
tions of  myotonic  muscles  to  electrical  and  other  stimuli.  It 
has  long  been  known  that  the  contraction  produced  by  electrical 
stimulation  is  slower,  and  relaxation  very  much  slower;  the 
latent  period,  however,  is  not  prolonged.  The  myotonic  re- 
laxation is  most  marked  after  very  strong,  and  especially  after 
strong  and  prolonged,  contractions,  tending  to  pass  off  as  the 
contraction  is  repeated.  Findlay  has  shown  that  certain 
stimuli,  such  as  a  tendon  jerk  or  a  minimal  and  momentary 


MYOTONIA  ATROPHICA  75 

faradic  or  galvanic  stimulus,  produce  a  normal  response,  whereas 
direct  percussion  or  a  stronger  or  longer  electrical  stimulus 
produce  a  myotonic  response.  Voluntary  movements  were 
found  to  be  at  first  slow,  then  gradually  increasing  in  rate  till 
they  were  quicker  than  those  of  the  examiner,  while  involun- 
tary movements  were  never  myotonic.  These  facts  do  not 
militate  against  the  hypothesis  that  the  morbid  process  lies 
in  the  muscle  fibres,  and  not  in  the  nervous  mechanism  of 
contraction. 

(j)  Myotonia  Atrophica. 

Aetiology. — This  disease  links  myotonia  with  the  myopathies. 
It  has  the  same  familial  characters  as  both.  The  myotonia  is 
usually  slight  in  degree  and  sometimes  has  not  been  noted 
till  late  adolescence,  but  in  most  cases  has  been  present  since 
infancy.  The  association  with  hereditary  cataract  in  some 
cases  seems  to  be  more  than  a  fortuitous  one.  The  disease 
corresponds  with  both  myotonia  and  myopathy  in  attacking 
males  more  frequently  than  females. 

Histology. — In  cases  where  pieces  of  the  affected  muscles  have 
been  examined  during  life  the  changes  described  under  myotonia 
and  under  myopathy  (q.v.)  are  present  in  varying  degree. 
The  muscle  fibres  tend  to  be  larger  and  more  rounded  than 
normal,  with  an  increase  in  the  number  of  sarcolemma  nuclei 
and  of  the  interstitial  connective  tissue.  In  one  case  some 
degeneration  of  the  dorsal  columns  of  the  cord  in  the  lumbar 
region  was  found. 

(k)  Myopathy. 

Aetiology. — In  this  disease  the  familial  character  is  very  well 
marked,  and  hereditary  transmission  has  been  frequently 
noted.  Males  are  more  frequently  attacked  than  females, 
especially  in  the  pseudo-hypertrophic  form.  In  this  the  trans- 
mission may  be  through  unaffected  females,  as  in  haemophilia 
and  congenital  night  blindness.  In  certain  cases  the  disease 
seems  to  have  been  started  by  some  trauma  or  febrile  illness, 
but  as  a  rule  there  is  no  obvious  cause  for  its  onset,  which  takes 
place  at  about  the  same  age  in  each  member  of  a  family  who 
is  affected.  Babinski  and  Onanoff  have  found  that  the  muscles 
most  differentiated  in  a  five-month  foetus  are  those  in  which 
myopathic  change  is  most  liable  to  occur,  and  suggest  that 


76     DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

these  muscles  have  less  vitality  than  those  which  are  laid 
down  later. 

Macroscopic. — The  disease  is  always  symmetrical  in  its 
attack  on  muscles,  and  tends  to  affect  the  muscles  at  the  roots 
of  the  limbs  more  than  those  more  distal.  Pseudo-hypertrophy 
is  most  commonly  seen  in  the  deltoid,  supra-  and  infra-spinati, 
and  in  the  gastrocnemii.  The  hyper trophied  muscles  are  firmer 
than  normal,  but  less  hard  on  contraction.  On  section  they 
appear  yellowish,  from  increase  of  fatty  tissue,  or  they  may  give 
the  appearance  of  a  mass  of  fat,  with  little  or  no  suggestion 
of  their  original  muscular  character. 

Histology. — Although  divided  into  several  clinical  types, 
myopathy  is  a  pathological  entity,  and  the  microscopical 
appearances  are  the  same  in  all  forms;  in  some  one  change 
predominates,  in  others  another,  but  all  varieties  of  the 
appearances  to  be  described  are  seen  in  almost  any  case  of 
the  disease. 

Apparently  the  earliest  change,  and  that  which  is  most 
commonly  found  in  pieces  of  muscle  excised  during  the  earliest 
stages  of  the  disease,  is  swelling  of  some  of  the  muscle  fibres 
and  increase  in  the  sarcolemma  nuclei.  The  fibres  may 
measure  from  150  /u  to  230  ^  across,  and  are  more  rounded 
in  outline  and  more  hyaline  in  appearance,  with  less  well- 
marked  striation.  This  appearance  has  been  ascribed  to 
swelling  of  the  sarcoplasm.  At  a  somewhat  later  stage  in  the 
disease  there  is  an  increase  in  thickness  of  the  connective- tissue 
septa  between  the  various  fibres  and  a  tendency  for  fat  to  be 
laid  down  here.  In  the  pseudo- hypertrophic  form  the  swollen 
muscles  show  a  very  great  deposition  of  fat  between  the  fibres, 
which  are  often  themselves  hypertrophied.  Except  in  the 
very  earliest  stages,  in  addition  to  large  fibres,  one  finds  a 
greater  or  smaller  number  of  very  small  ones,  and  it  has  been 
suggested  by  Marinesco  and  others  that  these  often  arise  from 
a  splitting  up  of  the  hypertrophied  fibres  into  smaller  bundles 
of  "  sarcostyles."  Thus,  in  longitudinal  sections  a  muscle 
fibre  is  sometimes  seen  to  break  up  into  two  or  three  segments, 
each  of  which  may  be  surrounded  by  a  large  number  of 
sarcolemma  nuclei.  Hyaline  degeneration  and  vacuolation 
of  the  hypertrophied  muscle  fibres  are  occasionally  seen.  It 
is  thus  clear  that  this  hypertrophy  is  a  morbid  change  with  a 


MYOPATHY 


77 


p^^i^p^-      4, 


'^^:  ^-   -  ' 


Fig.  i6. 
Muscle  in  the  pseudo-hypertrophic  form  of  myopathy. 


y%  AMYOTONIA  CONGENITA 

great  tendency  to  further  degeneration.  The  muscle  fibres  are 
also  seen  to  undergo  a  retrogressive  change  into  fibrous  tissue, 
especially  in  the  neighbourhood  of  the  tendinous  attachments. 
It  is  doubtful  whether  the  encroachment  of  tendinous  fibrous 
tissue  which  undoubtedly  takes  place  at  both  ends  of  an 
affected  muscle  is  due  to  this  retrograde  metaplasia  of  muscle 
fibres  or  to  their  atrophy  and  a  simultaneous  increase  of  the 
interstitial  connective  tissue.  Probably  both  these  factors  are 
at  work.  Eventually  the  picture  presented  is  that  of  a  few 
scattered  fibres,  some  larger  than  normal,  others  small,  atrophic, 
and  irregularly  shrunken,  separated  by  a  large  amount  of  fibrous 
and  fatty  tissue. 

Morbid  changes  have  been  described  in  the  motor  nerve 
endings,  but  the  muscle  spindles  have  been  found  intact  even 
in  advanced  stages  of  the  disease.  Changes  in  the  intra- 
muscular blood  vessels  are  constant.  Their  walls  are  thickened 
and  their  lumen  narrowed  by  connective-tissue  proliferation 
around  them.  Thromboses  have  been  described,  and  the 
adventitial  lymph  spaces  may  be  packed  with  newly-formed 
cells.  Changes  in  the  sympathetic  nerves  have  also  been 
noted. 

It  is  thus  possible  that  the  disease  is  primarily  one  of  the 
sympathetic  system,  and  that  inadequacy  of  blood  supply  to  a 
muscular  area  may  determine  the  changes  in  the  muscle  fibres. 
But  the  bulk  of  opinion  favours  the  hypothesis  that  the  muscles 
themselves  are  primarily  affected,  and  that  the  interstitial  and 
vascular  changes  are  secondary. 

(/)  Amyotonia  Congenita. 

This  rare  disease  was  first  described  by  Oppenheim,  who 
gave  it  the  name  of  myatonia,  but  as  this  name  is  apt  to  lead 
to  confusion,  English  writers  have  adopted  the  name  amyotonia. 

The  disease  is  congenital,  but  seems  to  have  no  tendency  to 
run  in  families.  Sylvestre  in  1909  reported  the  occurrence 
of  two  cases  in  a  family,  one  of  which  developed  Erb's  type  of 
myopathy  at  the  age  of  sixteen,  but  this  appears  to  be  the  only 
recorded  instance  of  the  kind,  and  a  sufficiently  large  number 
of  cases  of  the  disease  have  been  seen  to  make  it  fairly  certain 
that  it  has  no  familial  characters.  On  the  other  hand,  a 
considerable  number  of  the  patients  develop  definite  myopathy 


DEVELOPMENTAL  AND  FAMILIAL  DISEASES     79 

at  a  later  period  of  childhood,  and  both  on  this  account  and 
owing  to  the  similarity  in  the  histological  appearances  the 
disease  is  usually  classed  along  with  the  myopathies. 

Macroscopically,  the  limbs  are  slender  and  the  musculature 
very  soft.  The  hands  and  feet  are  peculiarly  long  and  delicate. 
On  section  the  muscles  are  yellowish,  and  are  distinguished 
with  difficulty  from  the  fat  which  lies  around  and  between  the 
muscle  bundles. 

Microscopically,  the  most  obvious  change  consists  in  the 
small  size  of  the  majority  of  the  fibres,  which  only  measure 
from  7  /^  to  12  /^  in  diameter.  But  among  them  there  are 
seen  a  few  fibres  of  giant  size  which  measure  up  to  140  /n. 
These  usually  lie  singly,  and  are  of  more  rounded  shape 
than  normal.  They  often  show  central  vacuolation,  and 
some  of  them  tend  to  split  longitudinally.  They  resemble 
in  every  way  the  large  fibres  seen  in  myopathic  muscles,  and 
like  them  are  less  numerous  in  cases  of  longer  standing. 

The  changes  in  the  central  nervous  system  are  equally 
definite,  but  do  not  appear  to  be  primary.  These  consist  in 
extreme  thinness  of  the  ventral  nerve  roots  and  diminution 
in  the  number  of  motor  cells  in  the  ventral  horns.  The 
nerve  roots  contain  fewer  fibres  than  normal,  and  these  are 
thin  and  poorly  myelinated.  These  appearances  seem  to 
be  accounted  for  by  the  presence  of  disease  of  the  muscles 
both  before  birth  and  during  the  first  few  months  of  extra- 
uterine life. 

REFERENCES 

Prenatal  Diseases  and  Abnormalities. 

Anton,  G.  :  In  Flatau,  Jacobsohn  and  Minor,  Handbuch  der  path.  Anat.  des 

Nervensy  stems,  1904. 
Ballantyne,    J.    W.:    Manual   of  Antenatal   Pathology   and  Hygiene:    The 

Embryo.     Edinburgh,  1904. 
Gombault  and  Riche:  Manuel  d' histologie  pathologique  (Cornil  and  Ranvier), 

vol.  iii.,  1907. 

Birth  Injuries. 

Taylor,  James:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910. 

Familial  and  Congenital  Diseases. 
(a)  Amaurotic  Family  Idiocy. 

Carlyll,    H.,   and   Mott,   F.   W.  :  Proc.  Roy.  Soc.   of  Med.,   1911.     Path., 

pp.  147-198. 
Hume,  W.  E.:  Rev.  Neur.  and  Psych.,  1914,  vol.  xii.,  p.  281. 
Russell,  J.  S.  Risien:  Allbutt  and  Rolleston,  System  of  Medicine,  1910, 

vol.  viii.,  p.  468. 


8o     DEVELOPMENTAL  AND  FAMILIAL  DISEASES 

{b)    Werdnig -Hoffmann  Paralysis. 

Batten,  F.  E.:  Brain.  1911,  vol.  xxxiii.,  p.  433. 

Batten,  F.  E.,  and  Holmes,  G.  :  Brain,  1912-13,  vol.  xxxv.,  p.  38. 

Krabbe,  K.  H.:  Brain,  1920,  vol.  xliii.,  p.  166. 

(c)  Friedreich's  Ataxia. 
Holmes,  Gordon:  Allbutt  and  RoUeston,  System  of  Medicine,  1910,  vol.  vii., 
P-  770- 

{d)  Progressive  Lenticular  Degeneration. 

Wilson,  S.  A.  Kinnier:  Brain,  1912,  vol.  xxxiv.,  p.  296. 

{e)  Huntington's  Chorea. 

Marie,  P.,  and  Lhermitte,  J.:  Rev.  Neur.,  1912,  vol.  xxiv.,  pp.  40-45. 
Russell,   J.  S.  Risien:  Allbutt  and   Rolleston,    System  of  Medicine,    1910, 
vol.  viii.,  p.  548. 

(/)  Peroneal  Atrophy. 

Batten,  F.  E.:  Allbutt  and  Rolleston,  System  of  Medicine,   1910,  vol.  vii. 

p.  71. 
Charcot  et  Marie:  Rev.  de  MSd.,  1886,  vol.  vi.,  p.  97. 
Tooth,  H.  H.:  Brain,  1888,  vol.  x.,  p.  243. 

(g)  Progressive  Hypertrophic  Interstitial  Neuritis  of  Children. 
Dejerine  et  Thomas:  Nouv.  Icon,  de  la  SalpSt.,  1906,  vol.  xix.    p.  477. 
Durante,   G.  :  Cornil  et  Ranvier,  Manuel  d' histologic  pathologique,   vol.  iii., 

Paris,  1907. 
ScHALLER,  W.  F.:  Arch.  int.  Med.,  1912,  vol.  x.,  p.  399. 

{h)  Family  Periodic  Paralysis. 

Buzzard,  E.  F.:  Lancet.  1901,  II.,  1565. 

Clarke  J.  Michell:  Allbutt  and  Rolleston,  System  of  Medicine,  1910,  vol.  vii., 
p.  65. 

{i,  j,  k)  Myotonia,  Myotonia  Atrophica,  Myopathy. 

Batten,  F.  E.:  Quarterly  Journal  of  Med.,  1910,  vol.  iii.,  p.  313. 
Collier,  J.:  Allbutt  and  Rolleston,  System  of  Medicine,  1910,  vol.  vii.,  p.  19. 
Findlay:  Qtiart.  Journ.  of  Med..  1912,  p.  495. 

Oppenheim":  Textbook  of  Nerv.  Disease  (trans.  A.  Bruce),  191 1,  p.  255. 
White,   W.   H.:   Allbutt  and  Rolleston,  System  of  Medicine,   1910,  vol.  vii., 
P-  25- 


CHAPTER  III 
INJURIES  TO  THE  NERVOUS  SYSTEM 

I.  Injuries  to  the  Brain  and  its  Coverings. 

Anatomical  considerations. — The  skull,  after  infancy,  may  be 
regarded  as  an  almost  rigid  bony  box,  with  one  large  opening, 
the  foramen  magnum,  and  several  smaller  ones,  of  which  the 
most  important  are  the  jugular  foramen,  the  sphenoidal  fissure, 
and  the  frontal,  occipital,  and  mastoid  openings  for  emissary 
veins.  Any  increase  of  the  intracranial  contents  is  therefore 
impossible,  but  the  bulk  of  any  one  constituent  may  increase 
if  at  the  same  time  there  is  a  diminution  of  another.  Thus,  an 
increase  of  the  size  of  the  brain  by  tumour,  abscess,  oedema, 
etc.,  may  be  compensated  for  by  a  diminution  of  the  amount  of 
cerebro-spinal  fluid  or  of  blood.  The  amount  of  blood  sup- 
plied by  the  arteries  cannot  vary  to  any  great  extent,  as  the 
vasomotor  centre  in  the  medulla  immediately  reacts  to  any 
diminution  in  the  blood  supply  to  the  brain  by  raising  the 
general  arterial  tension  and  thus  causing  the  intracranial 
vessels  to  be  supplied  at  a  higher  pressure.  (The  action  of  the 
vasomotor  centre  appears  to  be  regulated  by  the  reaction  of 
the  fluids  in  which  it  is  bathed,  a  very  slight  rise  in  H-ion 
concentration  sufficing  to  bring  it  into  activity.  It  may  thus 
be  stimulated  by  (i)  a  diminution  of  the  blood  supply  to  the 
medulla,  (2)  a  deficiency  in  oxygen  or  increase  in  carbon 
dioxide  in  the  blood,  or  (3)  by  a  general  acidosis.) 

It  follows  that  an  increase  in  the  size  of  the  brain  cannot 
be  compensated  for  by  diminution  in  the  amount  of  blood 
supplied  to  the  inside  of  the  cranium.  The  cerebro-spinal  fluid 
is  therefore  driven  out,  the  ventricles  become  more  slit-like, 
the  sulci  of  the  brain  narrowed,  and  the  cortex  of  the  brain 
more  closely  applied  to  the  cranial  vault.  There  is  also  an 
increase  in  the  amount  of  fluid  in  the  meshes  of  the  spinal 

8i  ,  6 


82  INJURIES  TO  THE  NERVOUS  SYSTEM 

arachnoid,  and  probably  some  slight  escape  along  the  lymphatics 
of  the  sheaths  of  the  spinal  nerves.  But,  unfortunately,  two 
vicious  circles  are  liable  to  occur  in  this  connection,  to  which 
attention  has  already  been  drawn  (p.  48). 

With  regard  to  the  anatomical  relationship  between  the  brain 
and  the  skull,  it  must  be  remembered  that  the  brain  proper  is 
nowhere  in  contact  with  the  dura  mater,  but  is  separated  from 
it  everywhere  by  the  water  cushion  formed  by  the  pia-arachnoid. 
The  large  cisternae  at  the  base  of  the  brain  form  a  water- 
bed  on  which  the  brain  rests,  and  protect  the  vulnerable 
cranial  nerves  and  vessels.  The  brain  is  also  protected 
from  undue  movement  inside  the  cranium  by  the  falx  cerebri 
and  tentorium  cerebelli,  which  prevent  lateral  and  vertical 
movement. 

Traumata  produce  lesions  of  the  brain  either  by  causing 
fractures  of  the  skull  or  by  jarring  the  brain  inside  the  skull 
and  thereby  damaging  its  tissues;  the  former  gives  rise 
to  wounds  or  lacerations  of  the  brain,  the  latter  to  con- 
cussion. 

Concussion  may  result  either  from  direct  or  indirect  violence. 
In  the  first  case,  it  is  most  often  due  to  blows  from  clubs,  falling 
stones,  bricks,  timber,  etc.,  or  to  falls  or  kicks  on  the  head.  As 
a  result  of  indirect  violence  it  may  be  due  to  jars  transmitted 
from  the  spine,  as  in  landing  on  the  heels  in  the  erect  position 
with  the  knees  straight,  or  landing  in  a  sitting  position  from  a 
height;  or  to  blows  on  the  chin  whereby  the  shock  is  trans- 
mitted to  the  middle  cranial  fossa  through  the  ramus  of  the 
lower  jaw.  It  may  also  be  caused  by  explosions.  It  varies 
greatly  in  degree  from  that  which  follows  but  a  momentary  loss 
of  consciousness  to  that  associated  with  prolonged  uncon- 
sciousness, retrograde  amnesia,  and  mental  confusion.  True 
concussion  may  be  associated  with  fractures  of  the  skull, 
especially  fractures  of  the  base  of  the  skull,  but  although  it  is 
often  associated  with  some  subarachnoid  haemorrhage,  it 
should  be  carefully  distinguished  from  the  results  of  com- 
pression due  to  bleeding  from  meningeal  vessels  into  the 
epidural  or  subdural  space. 

The  effects  on  the  brain  may  be  minimal:  either  no  macro- 
scopic lesion  is  observed,  or  there  may  be  slight  bruising  of 
the  cortex  over  a  larger  or  smaller  area  at  the  site  of    the 


CONCUSSION  OF  THE  BRAIN  83 

contusion,  or  on  the  opposite  surface  of  the  brain.  This  is 
spoken  of  as  the  contrecoup  effect.  It  is  probably  most  often  seen 
at  the  frontal  poles  from  bruises  on  the  occiput,  or  vice  versa, 
and  when  we  consider  the  way  in  which  the  cranial  cavity  is 
divided  up  by  dural  partitions,  this  is  not  difficult  to  under- 
stand. Subarachnoid  haemorrhage  is  usually  of  small  amount 
unless  the  large  veins  and  venous  lacunae  near  the  vertex  are 
torn,  in  which  case  the  escape  of  blood  may  be  large  enough 
to  give  rise  to  serious  pressure  effects.  The  arteries  of  the 
base  are  seldom  ruptured,  but  the  subcortical  vessels  may 
rupture  and  give  rise  to  haemorrhages  of  varying  size.  These 
are  most  frequently  found  in  the  frontal  region,  and  are  most 
likely  to  occur  in  subjects  with  degenerated  arteries.  Later 
effects  are  the  formation  of  areas  of  softening  either  cortical 
or  subcortical,  or  around  the  iter  of  Sylvius.  The  latter  is  a 
common  situation,  probably  because  this  part  of  the  brain 
is  often  bruised  by  the  sharp  edge  of  the  tentorium 
cerebelli. 

A  curious  sequel  is  the  occurrence  of  haemorrhages  in  the 
areas  of  softening  days,  weeks,  or  it  may  be  months  after  the 
original  injury.  Such  cases  are  not  very  uncommon  in  the 
literature,  and  in  a  large  proportion  of  them  the  haemorrhage 
is  found  in  the  region  of  the  iter  of  Sylvius. 

Another  unusual  result  of  concussion  is  internal  hydro- 
cephalus, the  causation  of  which  has  already  been  discussed 
(p.  47).  Cases  are  occasionally  seen  where  such  hydro- 
cephalus is  associated  with  a  cortical  softening  extending 
through  to  the  ventricle,  and  where  the  ventricular  fluid  under 
increasing  pressure  ruptures  the  softened  brain  substance  and 
escapes  into  the  subdural  space.  Damage  to  cranial  nerves 
often  results  from  concussion  (p.  94). 

Healing  of  the  bruised  area  in  the  cortex  and  meninges 
takes  place  later  with  the  formation  of  a  scar  in  which  an  area 
of  thickened  meninges  is  more  or  less  closely  bound  down  to 
sclerosed  cortex.  This  may  be  a  focus  of  increased  irritability, 
and  may  give  rise  to  fits  of  the  Jacksonian  type.  But  it  is 
probable  that  another  factor  than  the  presence  of  the  scar  is 
required  to  cause  these,  as  only  a  certain  percentage  of  patients 
with  scarred  brains  develop  epilepsy.  The  extent  of  the  local 
softenings  and  the  amount  of  damage  which  the  brain  suffers 


84  INJURIES  TO  THE  NERVOUS  SYSTEM 

from  any  traumatism  is  to  a  great  degree  dependent  on  the 
condition  of  the  arteries,  and  injuries  which  in  youth  would 
have  left  no  ill  effects  may,  in  later  life,  lead  to  gross  loss  of 
function. 

Wounds  of  the  Brain. 

In  civil  life  wounds  of  the  brain  are  most  often  caused  by 
blows  with  pointed  implements,  such  as  sharp  stones;  more 
rarely  they  are  due  to  falls  on  the  head  or  blows  from  large, 
heavy  objects.  When  such  blows  fracture  and  indent  the 
skull,  the  shock  is  usually  sufficient  to  cause  instant  death. 
There  are,  however,  many  cases  where,  without  any  fracture 
of  the  outer  table,  a  small  splinter  breaks  off  from  the  inner 
table  and  becomes  imbedded  in  the  brain.  In  such  cases  the 
general  concussion  effects  usually  overbalance  those  of  the 
local  lesion. 

The  chief  points  wherein  fractures  of  the  skull  differ  from 
concussions  are  their  tendency  to  cause  meningeal  haemorrhage 
at  the  site  of  the  fracture  and  the  frequency  with  which  they 
are  followed  by  septic  infection.  The  latter  may  occur  either 
directly  where  the  track  of  the  wound  passes  straight  through 
the  skull,  or  indirectly,  as  in  fractures  of  the  nasal  and  ethmoid 
bones,  or  fractures  of  the  base  of  the  skull,  when  a  channel 
may  be  established  between  the  outside  air  and  the  subdural 
space  through  the  bony  air  sinuses. 

Of  wounds  of  the  brain  in  war,  the  majority  are  either 
immediately  fatal  or  cause  death  within  a  few  hours.  But 
even  when  there  has  been  a  large  fracture  of  the  skull  and  very 
considerable  damage  to  the  brain  tissue,  a  surprisingly  large 
number  of  patients  live  for  days,  weeks  or  months,  and  either 
survive  with  some  loss  of  cerebral  faculties  or  ultimately 
succumb  to  septic  infection.  The  majority  of  the  wounds 
which  were  seen  at  the  base  and  home  hospitals  were  either 
those  caused  by  small  fragments  of  shrapnel,  which  had 
penetrated  the  skull,  or  by  bullets  which,  glancing  off  the  skull, 
had  caused  a  "  gutter  "  fracture.  In  the  former  cases  there 
was  more  or  less  bruising  of  brain  tissue  all  along  the  track 
of  the  missile,  and  sometimes  areas  of  haemorrhage  where 
smaller  or  larger  vessels  had  been  cut.  The  area  of  bruising  was 
usually  not  very  extensive,  and  might  be  considerably  larger 
on  the  cortex,  where  fragments  of  inner  table  had  been  driven 


WOUNDS  OF  THE  BRAIN  85 

in,  than   deeper  in  the  brain.     As  a  rule  bruising  did  not 
extend  more  than  i  cm.  from  the  track  of  the  missile. 

In  gutter  fractures  of  the  skull  the  effects  are  similar  to 
those  caused  by  blows  on  the  head,  with  certain  differences 
consequent  on  the  greater  velocity  of  the  missile,  which  causes 
the  fragments  of  the  inner  table  to  be  driven  more  deeply  into 
the  brain,  and  on  the  greater  liability  to  septic  infection  which 
is  shown  by  the  wounds  of  war.  Not  only  may  the  brain  be 
injured  by  fragments  of  bone,  but,  even  in  the  absence  of 
splintering  of  bone,  both  direct  and  contrecoup  bruising  may 
be  very  considerable.  As  has  already  been  noted,  such  areas 
of  bruised  and  softened  brain  may  extend  down  to  the  lateral 
ventricles.  They  form  funnel-shaped  areas  of  i  to  3  cm. 
in  diameter,  extending  for  a  similar  depth  from  the  cortex. 

In  every  case  within  twenty-four  hours  of  the  wound  some 
oedema  of  the  brain  tissues  around  the  damaged  area  occurs 
and  leads  to  enlargement  of  the  cerebral  substance.  As  a 
consequence  the  intracranial  pressure  rises,  and  if  there  is 
any  opening  in  the  skull,  softened  brain  matter  is  extruded 
through  it.  This  increase  in  intracranial  pressure  after  a 
wound  of  the  brain  has  been  thought  by  some  to  be  chiefly 
due  to  haemorrhage,  but  although  bleeding  may  be  a  pre- 
dominant factor,  it  is  by  no  means  necessarily  so,  and  many 
wounded  brains  have  been  examined  post  mortem  in  which 
there  was  no  evidence  of  any  but  petechial  haemorrhages. 
This  oedema  may  bring  about  a  fatal  result  or  it  may  subside, 
leaving  no  trace,  but  when  it  occurs  concurrently  with  septic 
infection  it  is  more  easy  for  organisms  to  penetrate  through 
the  brain  tissue  and  cause  encephalitis. 

Septic  infection  of  wounds  of  the  brain  may  start  (i)  at  the 
skin  edges,  (2)  in  the  middle  of  the  track,  where,  perhaps,  some 
hair  or  dirt  carried  in  with  the  missile  has  been  left  behind,  or 
(3)  around  the  missile,  when  this  remains  embedded  in  the 
brain.  The  nature  of  the  reaction  varies  with  the  type  of 
organism  present.  Streptococci  and  pneumococci  are  most 
liable  to  cause  rapidly  spreading  meningitis,  or  diffuse  encepha- 
litis; infection  with  the  gas  gangrene  bacilli  usually  causes 
a  very  acute  and  rapidly  fatal  encephalitis,  whereas  other 
organisms  may  cause  merely  a  local  infection,  resulting 
eventually   in  abscess   or   a    slowly   progressive    meningitis. 


86  INJURIES  TO  THE  NERVOUS  SYSTEM 

Streptothrix  infections  are  usually  mild.  When  the  ventricles 
are  infected  the  fatal  course  is  usually  rapid,  as  also  when  a 
purulent  meningitis  occurs  in  the  posterior  cranial  fossa, 
whereas  a  superficial  abscess,  or  area  of  meningitis  over  the 
vertex,  may  remain  circumscribed  and  give  rise  to  no  dangerous 
symptoms  for  weeks  or  months  after  the  wound. 

Infection  rarely  passes  through  an  intact  dura;  but  this 
accident  may  happen,  especially  in  the  neighbourhood  of  the 
large  venous  sinuses,  where  the  emissary  veins  are  more 
numerous.  In  this  case  the  sequence  of  events  is  probably 
first  an  infiltration  of  the  dura  mater,  starting  at  the  mouth  of 
a  venous  channel,  then  a  purulent  collection  in  the  subdural 
space,  and  lastly  a  purulent  leptomeningitis. 

It  is  probable  that  in  the  absence  of  sepsis  the  presence  of  a 
foreign  body  in  the  brain  causes  only  a  minimal  irritation,  as  it 
becomes  surrounded  with  a  layer  of  neuroglial  sclerosis  and  is 
thus  kept  from  direct  contact  with  neurons.  An  exception  to 
this  rule  is  afforded  by  metal  bodies  of  considerable  size  and 
weight  which  are  apt  to  shift  their  position  and  to  set  up  an 
aseptic  form  of  encephalitis,  giving  rise  to  clinical  signs  and 
symptoms  identical  with  those  of  cerebral  abscess. 

Wounds  may  injure  the  brain  or  its  coverings  indirectly. 
Thus,  a  wound  involving  the  common  carotid  or  internal 
carotid  artery  may  obstruct  the  blood  supply  to  the  parts  of  the 
brain  supplied  by  the  middle  and  anterior  cerebral  arteries. 
This  may  be  followed  by  hemiplegia  or  hemiparesis,  though 
not  necessarily.  In  such  cases  the  anterior  two-thirds  of  the 
cerebral  cortex  of  the  affected  side  have  been  found  congested, 
and  pinker  than  on  the  normal  side,  a  condition  of  "  diffuse 
infarction."  Wounds  over  the  superior  longitudinal  sinus 
frequently  lead  to  sinus  thrombosis,  and  by  obstructing  the 
venous  return  cause  oedema  and  temporary  loss  of  function  of 
the  cortex. 

Severe  wounds  involving  the  nasal  cavities  in  which  there  is 
a  considerable  degree  of  sepsis  not  infrequently  give  rise  to 
generalised  cerebro-spinal  meningitis.  This  is  usually  due 
to  the  streptococcus  or  pneumococcus,  which  probably  pass 
through  the  cribriform  plate  along  the  sheaths  of  the  olfactory 
nerves. 


INJURIES  TO  THE  NERVOUS  SYSTEM  87 

2.  Injuries  to  the  Spinal  Cord. 

Anatomical  considerations. — The  spinal  cord  is  suspended 
within  the  bony  walls  of  the  spinal  canal  by  very  loose  and 
indirect  attachments.  The  spinal  dura  mater,  which  is  thinner 
than  that  which  lines  the  cranial  vault,  is  not  firmly  applied  to 
the  bony  canal,  but  is  separated  from  it  by  the  epidural  space, 
which  is  filled  with  loose  areolar  tissue  and  a  plexus  of  veins. 
The  dura  is  fixed  to  the  spinal  canal  above  at  the  foramen 
magnum.  It  extends  down  as  a  loose  sheath  to  the  second 
sacral  vertebra,  whence  it  is  prolonged  as  a  fibrous  band,  the 
filum  terminale  externum,  to  the  periosteum  lining  the  lower 
end  of  the  sacral  canal.  It  is  loosely  attached  along  all  its 
extent  to  the  posterior  common  ligament  of  the  vertebrae, 
this  connection  being  firmest  in  the  upper  cervical  region, 
especially  opposite  the  body  of  the  axis,  and  also  in  the  lower 
lumbar  and  sacral  region.  The  sheath  of  dura  mater  is  also 
loosely  anchored  in  the  centre  of  the  vertebral  canal  by  the 
spinal  nerve  roots,  around  which  it  sends  prolongations  which 
are  attached  by  areolar  tissue  to  the  walls  of  the  inter- 
vertebral foramina.  It  is  thus  evident  that  in  the  lower 
cervical  and  thoracic  region  the  connections  between  the 
dural  sheath  and  the  bony  canal  in  which  it  lies  are  by  no 
means  firm. 

The  cord  is  suspended  within  this  sheath  both  by  the  spinal 
nerves  and  by  the  ligamentum  denticulatum,  which  may  be 
regarded  as  a  thickening  of  the  arachnoid  membrane  along  the 
sides  of  the  cord,  with  attachments  to  the  dura  mater  between 
the  points  of  exit  of  the  spinal  nerves.  Between  the  dura  and 
the  cord  lies  the  cushion  of  the  subarachnoid  space,  normally 
filled  with  cerebro-spinal  fluid.  The  subdural  space  is 
normally  non-existent,  as  the  membranes  which  form  its  outer 
and  inner  boundaries  are  closely  applied  to  one  another.  It. 
must  also  be  remembered  that  the  pia  mater  over  the  cord  is 
thicker  and  firmer  than  that  over  the  brain,  and  more  adherent 
to  the  nervous  tissue.  It  is  strengthened  by  longitudinal 
strands  of  fibrous  tissue,  which  are  specially  firm  over  the 
ventral  median  fissure. 

The  cord  is  subject  both  to  concussion  and  to  wounding  or 
laceration.      It   may  also    be  compressed  in  fracture-disloca- 


88  INJURIES  TO  THE  NJERVOUS  SYSTEM 

tion  of  the  spine,  and  is  specially  liable  to  injury  in 
caisson  disease.  These  various  lesions  will  be  considered  in 
order. 

Concussion. — The  forms  of  trauma  which  most  frequently 
cause  spinal  concussion  are  (i)  blows  on  the  back,  especially 
over  the  thoracic  region,  causing  abnormal  straightening  of  the 
spine;  (2)  falls  on  the  head,  which  cause  sudden  extreme 
backward  flexion  of  the  neck ;  and  (3)  wounds  by  bullets  and 
shell  fragments  which  strike  or  pierce  laterally  the  spinous 
processes.  In  the  first  two  cases  the  normal  thoracic  curve  of 
the  spine  is  straightened  out,  the  spinous  processes  and  laminae 
forming  a  fulcrum,  and  thus  the  vertebral  bodies  are  drawn 
away  from  each  other  and  the  intervertebral  discs  stretched 
or  torn  across.  The  articular  processes  are  sometimes  found 
fractured  in  such  cases,  with  little  or  no  displacement.  In 
case  (3)  the  momentary  distortion  is  a  lateral  one,  with  rotation 
around  a  fixed  point  supplied  by  the  vertebral  bodies  and 
intervertebral  discs.  If  any  bruising  happens  in  this  case  it 
affects  the  side  of  the  cord  from  which  the  missile  came, 
whereas  in  the  first  two  cases  the  dorsal  surface  of  the  cord  is 
primarily  affected. 

Macroscopically,  the  cord,  a  few  days  after  such  an  injury, 
is  swollen  at  the  level  of  the  lesion  and  for  a  varying  distance, 
usually  not  exceeding  a  couple  of  segments  above  and  below  it. 
The  pia-arachnoid  may  show  some  evidence  of  bruising,  or,  in 
cases  of  severe  lesion,  may  be  distended  by  yellowish  or  blood- 
stained fluid.  Unless  the  dura  mater  is  pierced  by  bony 
fragments,  the  pia  is  usually  intact.  On  section  at  the  level  of 
the  lesion  the  cord  may  present  all  degrees  of  change,  from 
complete  disintegration  into  a  pultaceous  custard-like  or 
sanious  material,  to  slight  oedema,  with  small  scattered 
haemorrhages;  these  may,  however,  be  completely  wanting. 

A  not  uncommon,  and  very  striking,  change  is  the  formation 
of  cylindrical  cavities,  of  one  to  two  millimetres  in  diameter, 
most  usually  in  the  ventral  part  of  one  or  both  dorsal  columns 
or  in  a  dorsal  horn.  They  may  in  slighter  cases  extend 
longitudinally  upwards  and  downwards  from  the  level  of  the 
lesion  for  a  distance  of  two  or  three  segments  in  either  direction ; 
and  in  severe  lesions  of  the  cord,  with  disintegration  of  its 
substance  at  the  level  of  the  lesion,  they  may  be  found  either 


CONCUSSION  OF  THE  SPINAL  CORD  89 

below  this  or  both  above  and  below.  Usually  they  do  not 
commence  in  the  softened  area,  but  in  healthier  tissue  a  few 
millimetres  away  from  it.  They  are  filled  with  a  greyish  or 
brownish  gelatinous  material,  and  are  thus  easily  visible  to 
the  naked  eye.  Examined  microscopically  their  contents  are 
seen  to  be  largely  blood  serum,  with  an  admixture  of  granular 
detritus  which  is  greatest  near  to  the  site  of  the  chief  lesion, 
and  of  granular  "  scavenging  "  cells,  which  also  line  their  walls. 
Blood  cells  may  be  found  in  them,  but  it  is  evident  that  they 
are  not  caused  by  haemorrhage.  That  they  are  formed  under 
pressure  is  clear  from  the  concentric  arrangement  of  the  tissues 
immediately  round  them,  and  from  the  way  in  which  they 
separate  the  nervous  tissues  without  destroying  them.  Various 
theories  have  been  put  forward  to  account  for  these  cavities, 
such  as  the  stasis  of  lymph  currents,  the  formation  of  exudates 
with  a  poisonous  action  on  the  nervous  elements,  or  vascular 
thrombosis  with  resulting  necrosis.  When  we  consider  that 
the  cord  is  always  swollen  and  oedematous  at  the  level  of  the 
lesion,  and  that  the  pia  mater  is  a  firm  membrane  and  is  almost 
always  intact  in  such  cases,  it  is  not  difficult  to  imagine  that 
the  serum  may,  in  trying  to  find  a  way  of  escape,  track  up  and 
down  the  cord  in  the  planes  of  least  resistance:  it  is  more 
difficult  to  formulate  a  reason  why  the  situation  is  so  constantly 
in  the  ventral  portions  of  the  dorsal  columns,  but  this  appears 
to  be  an  area  of  comparatively  poor  blood  supply,  and  thus 
may  form  a  locus  minor  is  resistantiae. 

Microscopically,  it  is  found  that  the  chief  incidence  of  the 
lesion  falls  on  the  axons  and  their  myelin  sheaths.  In  the 
more  softened  areas  both  of  these  are  completely  disintegrated, 
leaving  a  glial  network  containing  nothing  but  granules  of  fat 
contained  in  granular  corpuscles.  Where  there  is  less  destruc- 
tion of  tissue  the  axons  show  a  considerable  degree  of  swelling 
which  may  be  diffuse,  fusiform  or  moniliform,  so  that  they 
approach  the  size  of  a  normal  myelin  sheath.  Sometimes 
they  break  up  into  their  constituent  fibrils.  Their  sheaths 
may  be  thinned  out  or  broken  up  into  droplets,  and  the  glial 
space  containing  the  neuron  may  be  distended.  Small  areas 
with  these  appearances  are  scattered  irregularly  in  the  neigh- 
bourhood of  the  lesion,  often  affecting  the  outer  layers  of  the 
cord,  but  their  position  and  the  fact  that  they  are  separated 


90  INJURIES  TO  THE  NERVOUS  SYSTEM 

by  more  or  less  normal  tissue  suggest  that  they  are  not  due  to 
the  direct  influence  of  the  trauma,  but  more  probably  to  the 
effect  of  vibration  in  the  cord.  The  nerve  cells  show  a  varying 
amount  of  change  of  a  chromolytic  type,  which  is  probably 
secondary  to  the  lesions  of  the  axons. 

In  addition  to  the  changes  in  the  neurons,  oedema  of  the 
tissues  is  a  constant  feature.  It  is  seen  as  a  distension  of  the 
perivascular  spaces  and  a  general  separation  of  the  neurons, 
with,  at  times,  the  formation  of  small  cylindrical  cavities  which 
run  longitudinally,  usually  near  the  surface  of  the  cord  and 
especially  in  the  dorsal  columns.  A  glial  reaction  follows  at 
a  later  period,  but  probably  does  not  commence  until  after  the 
first  week  or  two. 

Haemorrhages  are  frequently  seen,  usually  petechial  in  size, 
and  more  often  in  the  grey  than  in  the  white  matter.  When 
they  are  larger  and  dominate  the  picture  the  condition  is 
described  as  "  haematomyelia,"  which  will  be  described  in  the 
next  chapter.  As  seen  in  the  wounds  of  war,  concussion  of 
the  cord  is  not  often  associated  with  gross  intramedullary 
haemorrhage,  probably  because  the  majority  of  soldiers 
are  young  men  with  healthy  arteries.  Suppuration  of  the 
cord  at  the  site  of  the  lesion  is  infrequent,  even  when  septic 
meningitis  is  present,  so  long  as  the  pia  mater  is  intact.  It  is 
unusual  in  such  cases  to  find  polymorphonuclear  leucocytes 
anywhere  except  in  the  sheaths  of  the  vessels  in  the  dorso- 
median  fissure. 

Wounds  and  injuries  of  the  spinal  cord  may  be  caused  in  a 
great  variety  of  ways.  First,  the  cord  may  be  cut  by  knife 
stabs,  or  wounded  by  bullets  or  fragments  of  shell-casing,  or  by 
spicules  of  bone  broken  off  in  their  passage.  Secondly,  and  more 
frequently,  it  is  injured  by  fractures  and  dislocations  of  the 
vertebrae  caused  by  falls  or  severe  blows  on  the  back,  or  by  the 
weight  of  fallen  masonry,  stones,  etc.,  under  which  the  spine 
bends  and  breaks.  Thirdly,  a  very  slight  trauma  is  sufficient 
to  produce  dislocation  of  the  vertebrae  in  diseases  or  malforma- 
tions of  the  spine.  Thus,  in  Pott's  disease  or  neoplasm  of  the 
vertebral  bodies,  the  sudden  onset  of  paraplegia  maybe  brought 
about  by  some  small  accident.  There  are  cases  of  imperfect 
ossification  of  the  odontoid  process  of  the  axis  where  this  has 
become  broken  off  by  a  very  slight  jar  or  sudden  voluntary 


FRACTURE-DISLOCATION  OF  THE  SPINE        91 

movement  of  the  head,  and  the  atlas  has  slipped  forward  on 
the  axis,  bruising  and  compressing  the  cord. 

The  first  of  these  varieties  of  trauma  differs  from  the  others 
in  causing  a  wound  which  lacerates  both  dura  and  pia  mater, 
and  has  a  channel  leading  from  the  cord  to  the  outside  air. 
Owing  to  this,  septic  myelitis  is  far  more  common  in  this  than 
in  any  of  the  other  varieties  of  trauma.  Also  because  of  the 
drainage  through  the  torn  pia  mater  oedema  of  the  cord  is  not 
so  frequent.  Lateral  hemisection  of  the  cord  (producing  the 
Brown-Sequard  syndrome)  is  more  common  in  knife  stabs  than 
in  any  other  form  of  injury,  but  it  is  also  frequently  caused  by 
gunshot  wounds.  In  knife  stabs,  as  has  been  pointed  out  by 
Head,  it  is  most  usual  for  both  dorsal  columns  to  be  divided, 
with  otherwise  a  fairly  exact  hemisection. 

Dislocations  and  fractures  of  the  vertebrae,  on  the  other 
hand,  usually  leave  the  dura  and  pia  mater  intact,  and  the 
condition  then  resembles  the  results  of  the  severer  forms  of 
concussion,  with  the  difference  that  the  nerve  roots  are  more 
apt  to  be  compressed  either  directly  by  bony  pressure  in  the 
intervertebral  foramina  or  by  the  clotting  of  effused  blood. 
The  haemorrhage  into  the  subdural  space  may  be  considerable, 
and  the  resulting  paralysis  fairly  extensive.  Haemorrhage 
outside  the  dura  is  less  likely  to  produce  of  itself  paralytic 
symptoms,  as  the  intervertebral  foramina  provide  a  ready 
means  of  escape  for  blood. 

In  the  majority  of  cases  of  fracture  or  dislocation  of  the 
spine  the  cord  is  injured  at  the  time  of  the  accident,  but  oedema 
and  haemorrhage  coming  on  within  the  next  few  days  may 
aggravate  the  damage  done.  Probably  after  this  period,  in 
the  majority  of  cases,  the  condition  of  the  cord  is  not  aggra- 
vated by  the  bony  compression,  but,  on  the  other  hand,  the 
canal  may  be  so  definitely  narrowed  at  the  level  of  the  lesion 
as  to  hinder  what  repair  of  the  cord  is  possible.  In  these  cases 
rapid  amelioration  of  symptoms  results  from  the  removal  of  the 
pressure  by  surgical  interference.  In  the  present  state  of  our 
knowledge  it  is  a  little  difficult  to  account  satisfactorily  for  this. 
Several  factors  are  involved,  to  all  of  which  in  greater  or  less 
degree  the  delay  in  the  return  of  function  is  attributable. 
There  may  be  obstruction  to  the  blood  supply  of  the  cord  at  'the 
level  of  the  lesion,  and  this  is  the  more  serious  owing  to  the 


92 


INJURIES  TO  THE  SPINAL  CORD 


^rSp 


/■#  N 


P'iG.    17. 

Sections  stained  by  the  Marchi  method  illustrating  the  ascending  degeneration 
the  spinal  cord  following  a  fracture-dislocation  in  the  mid-thoracic  region. 


CAISSON  DISEASE  93 

fact  that  longitudinal  anastomosis  between  the  arteries  of  the 
cord  is  completely  absent  within  the  substance  of  the  cord, 
although  it  exists  to  some  extent  in  the  pia  mater.  Further, 
in  all  cases  of  compression  of  the  cord  there  exists  some  oedema 
of  the  cord,  both  above  and  below  the  lesion. 

In  Weigert-Pal  stained  sections  of  the  cord  in  such  cases, 
we  are  struck  with  the  small  degree  of  ascending  and  descending 
degeneration  above  and  below  the  lesion,  as  compared  with  the 
almost  complete  absence  of  healthy  myelin  in  the  compressed 
segment.  It  appears,  therefore,  that  many  of  the  swollen  and 
fragmented  axis  cylinders  may  be  capable  of  preserving  the 
nutrition  of  the  distal  parts  of  the  neuron,  and  presumably 
may  also  be  capable  of  resuming  their  function  when  the  con- 
ditions at  the  site  of  the  lesion  are  improved.  Histologically , 
there  is  little  to  be  added  to  the  description  of  the  severer 
degrees  of  concussion  changes.  Where  sepsis  and  septic 
myelitis  occur,  there  is  an  invasion  of  the  cord  by  polymorpho- 
nuclear cells  and  mononuclear  cells  of  endothelial  and  con- 
nective-tissue origin.  These  are  at  first  seen  in  the  vicinity  of 
the  larger  blood  vessels,  but  when  the  myelitis  is  more  diffuse 
they  are  scattered  everywhere  in  the  cord.  In  the  slighter 
septic  cases  when  recovery  takes  place,  the  repair  is  largely 
accomplished  by  connective  tissue,  whereas  in  the  aseptic 
cases  the  new-formed  tissue  is  chiefly  of  neuroglial  origin. 

Caisson  Disease  {Diver's  Paralysis). 

Aetiology. — This  disease  has  been  proved,  both  clinically 
and  experimentally,  to  be  due  to  a  too  rapid  change  from  the 
air  pressure  in  the  caisson  to  that  of  the  outside  atmosphere. 
The  pressure  in  caissons  or  inside  a  diving  dress  may  be  any- 
thing from  one  to  five  additional  atmospheres,  and  at  such 
pressures  a  considerable  quantity  of  nitrogen  is  absorbed  both 
by  the  blood  and  by  the  tissues,  and  is  released  as  bubbles  of 
gas  when  the  pressure  is  reduced  too  quickly.  In  most  parts 
of  the  body  this  does  no  permanent  harm,  as  the  gas  is  rapidly 
absorbed  and  passed  out  of  the  lungs,  but  in  the  nervous 
system,  especially  in  the  spinal  cord,  the  effects  are  severe  and 
may  be  more  or  less  permanent. 

Schrotter's  view  of  the  pathology  of  the  disease  is  that  the 
bubbles  are  set  free  in  the  blood  vessels,  and  thus  produce  gas 


94  INJURIES  TO  THE  NERVOUS  SYSTEM 

embolism  and  infarction.  The  reason  why  the  white  matter 
of  the  cord  is  more  affected  than  the  grey  matter  Hes,  according 
to  this  view,  in  its  lower  vascularity,  and,  in  consequence,  its 
greater  vulnerability  by  vascular  obstruction.  On  the  other 
hand,  Vernon  has  shown  that  myelin  in  common  with  other 
fatty  tissues  in  the  body  has  a  much  greater  power  of  absorbing 
nitrogen  than  the  body  fluids  generally.  As  a  consequence,  the 
brain  and  spinal  cord  would  absorb  very  much  more  nitrogen 
in  virtue  of  their  high  myelin  content,  and  when  the  pressure 
is  lowered  the  gas  would  be  set  free,  not  in  the  blood  vessels, 
but  in  and  around  the  neurons,  thus  directly  breaking  up 
the  myelin  sheaths  and  causing  pressure  on  the  axons.  This 
view  gives  an  explanation  why  the  white  matter  of  the  cord  is 
especially  affected,  and  reconciles  the  changes  in  the  cord  with 
the  absence  of  infarctions  in  other  organs. 

Histologically ,  the  disease  is  characterised  by  multiple  small 
softenings  in  the  cord,  chiefly  in  the  white  matter.  At  the 
centre  of  the  softened  area  the  tissues  are  broken  up,  and  very 
little  of  the  original  structure  remains.  Towards  the  outer 
parts  the  myelin  is  fragmented  and  degenerated,  and  the  axis 
cylinders  are  often  greatly  swollen,  sometimes  to  twenty  times 
their  natural  size.  There  is  little  vascular  reaction,  and  the 
processes  of  repair  are  mainly  undertaken  by  neuroglial 
elements. 

3.  Injuries  to  Nerves. 

The  peripheral  nerves  are  less  protected  from  injury  than 
the  brain  and  spinal  cord — in  fact,  some  of  them  lie  in  very 
exposed  positions;  but  the  limited  paralysis  caused,  and  the 
probability  of  recovery,  make  lesions  to  nerves  much  less  im- 
portant than  lesions  of  similar  extent  in  the  spinal  cord.  In  a 
large  proportion  of  cases  the  function  of  the  nerve  is  not  com- 
pletely lost,  and  even  where  complete  severance  of  the  nerve 
has  occurred  some  degree  of  function  may  be  restored  within  a 
year  if  the  conditions  are  favourable.  This  does  not  hold  good 
for  cases  of  injury  of  a  sensory  nerve  between  its  ganglion  and 
the  central  nervous  system,  as  the  fibres  in  that  case  are 
centripetal,  and  degenerate  into  the  tracts  of  the  cord  or  brain 
where  no  regeneration  is  known  to  take  place.  Thus,  deafness 
due  to  lesion  of  the  auditory  nerve  in  the  internal  auditory  canal 
cannot  be  cured.     The  olfactory  and  optic  nerves  hold  a  similar 


INJURIES  TO  NERVES  95 

relation  to  their  cells  of  origin,  though  they  are  not  correctly 
spoken  of  as  peripheral  nerves,  as  in  structure  and  development 
they  are  very  different.  In  certain  birth  paralyses,  which  will 
be  mentioned  later,  the  lesion  may  affect  the  spinal  nerve  roots 
between  the  dorsal  root  ganglion  and  the  cord,  and  in  these 
cases,  although  theoretically  the  motor  root  may  recover,  the 
sensory  cannot ;  as  a  matter  of  fact,  recovery  of  motor  power  is 
exceptional. 


X 


'"^^op 


Fig.  18. 

Jj  peripheral  nerve  undergoing  degeneration  as  the  result  of  pressure,  stained 
by  the  Marchi  method. 

Injuries  to  peripheral  nerves  are  most  usefully  classified 
from  a  pathological  standpoint  into  those  in  which  the  nerve 
is  injured  by  blow^  on  it  or  by  damage  to  neighbouring  tissues 
in  such  a  way  that  its  sheath  is  not  ruptured,  and  those  in 
which  the  whole  nerve  or  a  part  of  it  is  cut  or  torn  across. 

In  the  former  case  there  will  be  some  effusion  of  blood  or 
lymph  into  and  around  the  sheath  of  the  nerve.  The  nerve 
fibres  may  be  injured  to  a  greater  or  less  degree.  In  the  slighter 
cases  the  axis  cylinders  are  relatively  intact,  although  there 


Fig.  19. 

{a)  A  low-power  photograph  of  an  excised  portion  of  nerve  which  had  undergone 
changes  of  a  fibrotic  character  following  the  passage  of  a  bullet  through  the  tissues 
in  its  immediate  vicinity.  Photograph  of  sections  taken  (6)  just  above  and 
(c)  below  the  site  of  injury  stained  by  the  Bielschowsky  method.  In  (c)  there 
are  very  few  axis  cyUnders  remaining. 


INJURIES  TO  NERVES  97 

may  be  a  considerable  degree  of  damage  to  the  myelin  sheaths, 
many  of  which  break  up  into  fatty  substances  and  are  absorbed. 
The  resulting  paralysis  will  then  pass  off  completely  in  the 
course  of  days  or  weeks,  unless  the  effusion  of  blood  or  lymph 
within  the  sheath  of  the  nerve  or  the  resulting  fibrous  cicatrix 
interferes  with  the  reparative  processes.  In  more  severe  cases 
some  of  the  axis  cylinders  may  be  so  damaged  that  they  become 
unable  to  carry  on  the  nutrition  of  the  peripheral  part  of  the 
nerve,  and  Wallerian  degeneration  results.  In  some  cases  the 
whole  nerve  is  affected  in  this  way,  in  others  only  a  smaller 
or  larger  proportion  of  the  fibres.  In  the  latter  case,  return  of 
function  takes  place  in  two  stages,  between  which  there  is  an 
interval  of  months  or  years,  as  the  less  damaged  fibres  resume 
function  rapidly,  whereas  those  more  severely  injured  give  rise 
to  new  fibres  which  must  grow  from  the  level  of  the  lesion  to 
the  nerve  endings  in  skin,  muscle  and  tendon  before  function 
can  be  restored. 

When  the  nerve  and  its  sheath  are  cut  or  torn  across,  there 
must  be  rupture  of  the  axis  cylinders  with  consequent  Wallerian 
degeneration  in  the  peripheral  segment  of  the  nerve.  The  pro- 
cesses of  nerve  regeneration  then  take  place  with  the  formation 
of  end  bulbs  on  the  upper  and  lower  cut  ends,  which  fuse  to- 
gether if  the  ends  are  kept  in  contact,  and  conduct  the  young 
neuro-fibrils  to  the  old  neurolemma  sheaths  of  the  peripheral 
segment. 

When  the  ends  are  separated  by  a  gap,  some  of  the  out- 
growing nerve-fibre  processes  may  leave  the  bulb  on  the  proximal 
end  and  pass  along  the  planes  of  the  intervening  fibrous  tissue 
to  reach  the  bulb  on  the  lower  end,  but  the  number  of  fibres 
which  pass  across  in  this  way  is  rarely  large  enough  to  lead  to 
useful  return  of  function. 

Although  the  formation  of  end  bulbs  usually  occurs,  they 
may  be  absent  in  cases  where  sepsis  interferes  with  the  normal 
processes  of  recovery  and  checks  the  proliferation  of  the  nervous 
elements.  Sepsis  may  even  cause  an  ascending  neuritis  in 
the  proximal  end  of  the  nerve,  which  may  extend  up  the  nerve 
for  several  inches  from  the  level  of  the  lesion.  Evidence 
of  this  is  afforded  histologically  by  degeneration  of  the  axis 
cylinder  and  myelin  sheath,  and  by  inflammatory  changes  in 
the  peri-  and  endo-neurium. 

7 


'^^^ 


Fig.  20. 

Sections  of  ulnar  nerve  seven  months  after  a  wound  that  severed  it.  a,  A 
longitudinal  section  immediately  above  the  wound,  showing  a  few  of  the 
original  well-myelinated  fibres,  with  many  finely  myelinated  new  fibres 
running  in  all  directions,  b,  Centre  of  neuroma  bulb  separating  ends. 
c.  Lower  end.  A  very  few  myelinated  fibres  have  regained  the  nerve  tracts 
(neurolemma  channels)  of  the  lower  end.     Stained  by  the  Weigert-Pal  method. 


INJURIES  TO  NERVES 


99 


Fig.  21. 

Sections  of  an  ulnar  nerve  five  months  after  section  by  wound,  stained  by  Biel- 
schowsky's  method,  a,  at  upper  end  of  neuroma  just  above  level  of  injury. 
b,  in  the  middle  of  the  neuroma,  c.  Lower  end,  a  few  fibres  having  regained 
the  neurolemmal  tracts  of  the  nerve  beyond  the  injury. 


100  INJURIES  TO  CRANIAL  NERVES 

Where  the  nerve  is  liable  to  long-continued  pressure  or 
irritation,  a  condition  of  interstitial  neuritis  may  be  produced. 
In  this  case  the  degeneration  in  the  nerve  fibres  is  secondary 
to  overgrowth  of  the  fibrous  tissue  forming  the  peri-  and  endo- 
neurium.  In  the  earlier  stages  the  condition  is  one  of  loss  of 
function  without  destruction  of  the  axis  cylinders,  and  recovery 
is  usually  rapid  and  complete.  But  in  some  cases  the  fibrous 
tissue  becomes  so  dense  and  firm  that  it  is  very  slowly  absorbed, 
even  under  the  most  favourable  conditions,  and  the  functional 
restoration  of  the  nerve  is  correspondingly  slow. 

The  cranial  nerves  are  protected  from  direct  injury  in  their 
intracranial  course,  but  are  liable  to  injury  both  in  their  bony 
canals  and  in  their  extracranial  portion.  They  may  also  be 
pressed  on  by  effused  blood  in  the  meningeal  haemorrhage 
resulting  from  injuries.  The  nerves  of  special  sense  (I.,  11. , 
VIII.,  and  the  pars  intermedia  of  VII.)  are  particularly  liable 
to  such  injuries,  as  is  also  the  facial  nerve,  both  in  its  bony 
canal  and  outside  the  skull.  The  olfactory  nerves  are  often 
torn  across  in  severe  blows  or  falls  on  the  head,  resulting  in 
complete  loss  of  the  sense  of  smell.  The  optic  nerves  may  be 
directly  injured  by  puncture  wounds  of  the  orbit  or  by  frag- 
ments of  metal  in  steel  works,  or  pieces  of  shell  or  bomb-casing. 
The  chiasma  or  the  optic  nerve  or  tract  may  also  be  pressed 
on  by  meningeal  haemorrhages.  The  facial  and  auditory 
nerves  and  the  pars  intermedia  are  very  frequently  involved  in 
fractures  of  the  base  of  the  brain  which  pass  through  the  petrous 
portion  of  the  temporal  bone.  Fortunately,  this  usually 
happens  on  one  side  only,  as  it  results  in  complete  loss  of 
hearing  and  facial  paralysis.  Tho^  facial  is  also  liable  to  injury 
in  its  course  through  the  parotid  gland,  either  by  severe  blows 
of  the  fist  or  by  sabre  wounds  (which  is  a  fairly  common  in- 
cident in  duelling  in  Germany).  The  other  cranial  nerves  are 
less  liable  to  injury,  but  the  spinal  accessory  in  the  neck  is  not 
infrequently  injured  in  surgical  operations. 

Injuries  to  the  brachial  plexus  or  its  roots  are  not  uncommon, 
and  two  forms  are  sufficiently  classical  to  be  called  after  the 
neurologists  who  first  investigated  them.  These  are  the  Erh- 
Duchenne  and  the  Klumpke  types  of  paralysis.  The  former 
name  is  given  to  lesions  of  the  upper  trunk  of  the  brachial 
plexus,  or  to  the  fifth  and  sixth  cervical  roots  which  form  it. 


INJURIES  TO  THE  BRACHIAL  PI;feXlJS    i  [Vx^yJ^,] 

This  may  be  produced  in  a  variety  of  ways.  The  commonest 
and  classic  cause  is  a  fall  on  the  shoulder  of  such  a  kind  that 
the  latter  is  forcibly  separated  from  the  head  (Erb),  or  it  may 
occur  as  a  birth  injury  in  breech  presentations  from  traction 
on  the  shoulders  or  arms  before  the  head  is  born  (Duchenne). 
It  may  also  be  caused  by  pressure  on  the  shoulder,  as  by  a 
haversack  or  pack  strap.  In  this  case  it  is  probably  due  to  the 
nerve  being  nipped  between  the  clavicle  and  the  first  rib.  In 
the  Klumpke  type  of  paralysis  the  inferior  trunk  of  the  plexus 
is  injured,  or  the  eighth  cervical  and  first  thoracic  roots  torn 
across  close  to  their  point  of  emergence  from  the  cord.  It  is 
usually  produced  by  traction  on  the  arm  in  an  upward  and 
outward  direction,  as  when  the  hand  is  caught  in  machinery. 
When  the  roots  are  torn  close  to  the  cord  the  fibres  going  to  the 
cervical  sympathetic  are  destroyed.  Paralysis  of  the  eighth 
cervical  root  alone  is  often  associated  with  the  presence  of 
cervical  ribs,  and  may  come  on  after  some  injury  or  strain. 
In  this  condition  either  the  cervical  rib,  or  the  fibrous  band 
which  joins  it  to  the  first  rib,  rubs  against  the  nerve  root.  It 
is  to  be  noted  that  the  longer  the  rib  is,  the  less  likely  is  it  to 
produce  paralysis.  Paralysis  of  the  plexus  as  a  whole,  or  the 
greater  part  of  it,  may  result  from  crushing,  associated  with 
fracture  of  the  clavicle. 

Apart  from  penetrating  wounds  of  the  arm,  certain  forms  of 
injuries  to  the  brachial  nerves  are  fairly  common.  Such  are  the 
circumflex  nerve  paralysis  resulting  from  dislocation  of  the 
shoulder  joint  or  severe  wrenching  of  the  arm  at  the  joint,  and 
the  muscuh-spiral  palsy  which  may  result  when  the  arm  hangs 
over  the  side  of  a  bench  or  table  during  sleep,  the  so-called 
"  drunkard's  palsy,"  or  which  may  be  caused  by  long-continued 
pressure  in  "  crutch  paralysis."  The  musculo-spiral  is  also 
very  liable  to  injury  by  the  blow  of  a  stick  on  the  outside  of 
the  arm,  or  by  sword  wounds.  The  ulnar  nerve,  owing  to  its 
intimate  connection  with  the  capsule  of  the  elbow  joint,  is  often 
injured  in  dislocations  or  fractures  of  the  joint,  and  its  exposed 
position  renders  it  specially  liable  to  develop  a  chronic 
interstitial  neuritis. 

In  the  lower  limb  traumatic  paralysis  is  uncommon,  and  when 
it  does  occur  it  is  usually  the  external  popliteal  nerve  which  is 
affected.     This  branch  of  the  sciatic  seems  particularly  liable 


102  INJURIES  TO  THE  NERVOUS  SYSTEM 

to  injury  even  in  the  pelvis,  as  it  is  chiefly  affected  in  the 
paralysis  of  childbirth,  which  is  produced  by  the  pressure  of  the 
foetal  head  in  the  pelvis.  It  may  also  be  paralysed  by  injuries 
to  the  head  or  neck  of  the  fibula,  or  by  the  prolonged  kneeling 
necessitated  by  certain  occupations  such  as  asphalter's 
drop-foot. 

REFERENCES 

Babonneix  et  Voisin:  Paralysie  radiculaire  type  Erb,  d'origine  obst6tricale. 

Gaz.  des  Hop.  de  Paris,  1909,  vol.  Ixxxii.,  p.  719. 
Boycott,  A.  E.,  Damant,  G.  C.  C,  and  Haldane,  J.  S.:  The  Prevention  of 

Compressed-aii  Illness,  Journal  of  Hygiene,  vol.  viii.,  1908,  p.  342;  Quart. 

Journ.  of  Med.,  vol.  i.,  1908,  p.  348;  Journ.  of  Path,  and  Bact.,  vol.  xii., 

1908,  p.  507. 
D^jerine-Klumpke:   Paralysie  radiculaire  des  plexus  brachial.     Rev.  prat. 

de  trav.  de  Mid.,  1898,  vol.  Iv.,  p.  23. 
Heller  Mager  und  v.  Schrotter:  Luftdruckerkrangungen.     Vienna,  1900. 
Hill,  Leonard:  Caisson  Sickness.     London,   1912. 
Holmes,  Gordon:  The  Spinal  Injuries  of  Warfare,   B.M.J.,    1915,    vol.  ii., 

pp.  769,  815,  855. 
Holmes,  G.,  and  Sargent,  P.:  Injuries  of  the  Superior  Longitudinal  Sinus, 

B.M.J..  1915,  vol.  ii.,  p.  493. 
MoTT.  F.  W. :  Effects  of  High  Explosives  on  the  Central  Nervous  System, 

(Lettsonian  Lectures,  1916),  Archives  of  Neurology,  1918,  vol.  vii. 


CHAPTER  IV 

CIRCULATORY  DISTURBANCES  OF  THE  BRAIN 
AND  SPINAL  CORD 

The  physiology  of  the  cerebral  circulation  has  been  the  subject 
of  much  discussion  for  many  years,  and  there  are  yet  many 
questions  in  connection  with  it  which  have  not  received  a  final 
answer.  The  pathology  of  the  cerebral  circulation  is  still 
more  complex,  but  recent  work  has  cleared  up  some  of  the 
earlier  misconceptions.  For  instance,  it  is  no  longer  permissible 
to  take  the  post-mortem  appearance  of  the  cerebral  and  menin- 
geal vessels  after  the  skull  cap  has  been  removed  as  indicative 
of  the  circulatory  condition  when  the  brain  was  still  pulsating 
in  the  closed  cranium.  Little  importance  is,  therefore,  attached 
to  hyperaemia  or  anaemia  of  the  brain  tissue  after  death,  and 
"  cerebral  congestion  "  as  a  diagnosis  has  ceased  to  satisfy  the 
scientific  pathologist. 

According  to  modern  teaching  the  amount  of  blood  con- 
tained in  the  cranial  cavity  can  vary  but  little,  and  arterial 
hyperaemia  has  no  significance  as  a  morbid  state.  When  the 
current  of  arterial  blood  in  the  brain  is  increased  the  amount 
of  venous  blood  is  proportionately  diminished.  In  the  same 
way,  venous  congestion  of  the  brain  is  associated  with  a 
diminished  supply  of  arterial  blood.  Cerebral  hyperaemia 
depends,  therefore,  on  a  general  rise  in  arterial  pressure,  and 
exerts  its  influence,  not  so  much  by  increasing  the  blood 
content  of  the  brain,  as  by  sending  blood  more  rapidly  through 
the  cerebral  vessels.  Cerebral  hyperaemia  is  associated  with 
an  improved  quality  of  blood  in  the  brain,  and,  therefore,  with 
greater  cerebral  activity.  Probably  the  initiation  of  cerebral 
activity  under  normal  conditions  brings  about  the  rise  in  the 
arterial  pressure  through  stimulation  of  the  bulbar  vasomotor 
centres.  The  results  of  cerebral  hyperaemia  are  increased 
mental  energy  combined  with  a  sense  of  well-being. 

103 


104  CEREBRAL  ANAEMIA 

Cerebral  anaemia  may  be  a  pathological  condition,  and  may 
be  either  local  or  general.  The  results  are  very  similar,  whether 
they  arise  from  a  diminution  of  the  arterial  blood  supply  or 
from  venous  congestion  produced  by  obstruction  to  the  venous 
outflow.  General  anaemia  of  the  brain  is  brought  about  by 
cardiac  failure,  great  loss  of  blood,  respiratory  embarrassment, 
or  determination  of  blood  to  the  abdomen ;  on  the  other  hand, 
local  anaemia  may  result  from  embolism  or  thrombosis  of  a 
cerebral  artery,  meningeal  or  cerebral  haemorrhage,  com- 
pression by  tumours,  etc. 

The  effects  of  cerebral  anaemia  vary  according  to  whether 
it  is  local  or  general,  partial  or  complete,  slow  or  sudden  in 
onset.  Local  anaemia  is  considered  below.  When  general 
cerebral  anaemia  is  rapidly  or  suddenly  produced  loss  of 
consciousness  is  the  first  result,  and  this  may  be  followed 
by  epileptic  convulsions,  dilatation  of  pupils,  slowing  of  pulse 
and  respiration  and  rise  of  arterial  pressure.  If  the  anaemia 
continues  the  pulse  becomes  rapid,  arterial  pressure  falls,  and 
respiration  ceases.  It  seems,  therefore,  that  cerebral  anaemia 
in  the  first  instance  increases  the  excitability  of  the  bulbar 
centres,  while  it  rapidly  destroys  that  of  the  cortex. 

When  ligatures  are  placed  simultaneously  on  both  carotid 
and  both  vertebral  arteries  of  a  dog  the  animal  survives,  but  a 
condition  of  idiocy  is  established  similar  to  that  of  the  de- 
cerebrate animal.  Histological  examination  of  the  cortex 
twenty-four  hours  after  the  operation  reveals  definite  changes 
in  the  nerve  cells.  They  are  swollen,  their  protoplasm  is 
diffusely  stained  with  methylene  blue,  and  the  Nissl  granules 
have  disappeared  (p.  13).  In  higher  animals,  such  as  the 
monkey,  the  sudden  ligature  of  all  four  arteries  is  followed  by 
death,  and  this  would  doubtless  obtain  in  human  beings.  As 
a  matter  of  fact,  it  is  unsafe  to  tie  one  carotid  artery  in  man 
unless  the  process  is  carried  out  slowly. 

The  results  of  a  slowly  progressive  cerebral  anaemia  in 
human  pathology  are  illustrated  by  what  occurs  in  extensive 
atheroma  of  the  cerebral  arteries.  The  cortical  cells  become 
starved  and  atrophic,  the  nervous  tracts  degenerate,  and  minute 
areas  of  liquefying  necrosis  may  be  seen  in  the  central  brain 
substance  surrounding  the  diseased  arterioles.  Such  cases 
display  progressive  signs  of  dementia  and  impairment  of  motor 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN    105 

and  sensory  function.  They  may  be  classed  under  senile  dementia 
or  chronic  progressive  double  hemiplegia,  according  to  the  pre- 
dominance of  mental  or  physical  deterioration. 

I.  Ischaemic  Softening  of  the  Brain. 

This  form  of  softening  is  limited  to  the  area  of  distribution 
of  a  particular  artery,  and  is  dependent  on  the  obliteration  of 
the  circulation  through  that  artery.  It  is  identical  with  the 
infarcts  of  other  organs,  such  as  the  spleen,  the  kidney,  the 
lung,  etc.,  and  differs  only  from  the  latter  on  account  of  the 
peculiar  structure  of  the  brain  tissue.  The  obliteration  of  the 
arterial  lumen  is  brought  about  in  the  majority  of  instances 
either  by  the  lodgment  of  an  embolus  or  by  thrombosis  taking 
place  as  the  result  of  disease  in  the  vessel  wall.  The  changes 
in  the  vessel  wall  may  be  of  an  atheromatous  character  or  due 
to  arteritis,  generally  syphilitic  in  origin.  It  should  not  be 
forgotten  that  other  infections — those  of  tuberculosis  and  the 
acute  specific  fevers,  for  instance — may  occasionally  cause 
arteritis.  Sometimes,  though  comparatively  rarely,  the  inter- 
ference with  the  circulation  is  brought  about  by  pressure  on  the 
vessel  from  without — for  instance,  by  the  presence  of  a  tumour. 
Thrombosis  is  naturally  favoured  by  any  increase  in  the 
coagulability  of  the  blood  or  by  diminution  in  the  rate  of 
blood  flow. 

In  the  case  of  an  embolus,  which  may  be  a  small  mass  of 
fibrin,  a  portion  of  a  diseased  cardiac  valve,  or  a  fragment  of 
diseased  intima  from  the  aorta  or  one  of  its  large  branches,  the 
arrest  of  circulation  is  generally  brought  about  by  the  lodgment 
of  the  offending  particle  at  or  near  an  arterial  bifurcation.  The 
source  of  the  embolus  must  be  sought  for  either  in  the  pul- 
monary circulation,  the  left  side  of  the  heart,  the  ascending 
aorta  or  the  branches  arising  from  the  aortic  arch.  It  appears 
to  be  more  frequent  for  the  embolus  to  pass  into  the  left 
carotid  artery,  and  therefore  to  cause  ischaemic  softening  more 
often  on  the  left  than  on  the  right  side  of  the  brain.  As  a 
matter  of  experience,  the  middle  cerebral  artery  on  the  left  side 
is  more  often  affected  in  this  way  than  any  other  vessel. 

The  position  of  an  area  of  ischaemic  softening  depends  upon 
the  artery  obliterated,  and  its  size  is  determined  by  the  calibre 
of  the  artery.     Thus,  if  the  main  trunk  of  the  middle  cerebral 


io6    CIRCULATORY  DISTURBANCES  OF  THE  BRAIN 


Fig.  22. 

Cerebral  softening,  the  result  of  embolism  of  the  left  middle  cerebral  artery,  in 
a  case  of  aortic  valvular  disease. 


THROMBOSIS  OF  CEREBRAL  ARTERIES 


107 


artery  is  blocked  before  the  perforating  branches  are  given  off, 
softening  will  ensue  in  the  basal  ganglia  and  internal  capsule, 
as  well  as  in  parts  of  the  cortex  around  the  fissures  of  Rolando 
and  Sylvius.  On  the  other  hand,  if  the  interference  with 
circulation  is  situated  beyond  the  origin  of  the  perforating 
arteries,  only  the  cortical  substance  will  be  affected.  Some- 
times, when  smaller  branches  are  the  seat  of  thrombosis  or 
embolism,  only  limited  areas  of  the  cortex  undergo  the  softening 
process.  Atheroma  of  the  basilar  artery  is  common  in 
advanced  life,  with  the  result  that  pontine  thrombosis  due  to 
blocking  of  one  of  its  branches  is  of  frequent  occurrence. 


Fig.  23. 
Thrombosis  of  the  left  posterior  cerebral  artery. 


As  a  matter  of  fact,  necrosis  does  not  take  place  throughout 
the  whole  of  the  territory  supplied  by  the  blocked  artery,  owing 
to  the  fact  that,  although  the  cerebral  arteries  are  to  some 
extent  terminal  vessels,  there  is  a  certain  amount  of  over- 
lapping of  one  arterial  territory  with  another.  The  greatest 
degree  of  destruction  of  brain  tissue  from  the  obliteration  of 
one  middle  cerebral  artery  seems  to  occur  in  cases  of  gross 
aortic  incompetence,  and  is  probably  due  to  the  low  dia- 
stolic blood  pressure  in  this  condition,  and  the  resulting 
poverty  of  the  capillary  blood  supply  which  reaches  the 
damaged  area  from  the  anterior  and  posterior  cerebral 
arteries. 


io8       THROMBOSIS  OF  CEREBRAL  ARTERIES 


Fig.  2^. 
Softening  in  the  region  of  the  lenticular  nucleus. 


Fig.  25. 

Pontine  thrombosis  due  to  disease  of  the  basilar  artery  or  its  branches. 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN     109 

Morbid  anatomy. — Recent  softening  cannot  be  satisfactorily 
investigated  if  the  brain  is  examined  in  a  fresh  condition.  In 
fact,  it  may  very  easily  escape  detection  if  the  organ  is  cut 
up  on  the  post-mortem  table.  On  the  other  hand,  after 
hardening  in  10  per  cent,  formalin,  even  recent  patches  of 
softening  are  readily  traced. 

The  appearances  of  a  softened  area  vary  with  the  age  of 
the  lesion,  and  with  more  minute  differences  dependent  on  the 
blood  supply  of  the  region  affected. 

Recent  softening. — That  part  of  the  cerebral  hemisphere  from 
which  the  blood  supply  has  been  recently  cut  off  is  generally 
somewhat  swollen,  owing  to  the  fact  that  it  is  the  seat  of  a 
serous  infiltration.     If  the  patch  is  on  the  surface,  the  con- 


FlG.   26. 
Cerebral  thrombosis.     The  shrunken  convolutions  have  a  yellowish  tinge. 

volutions  are  enlarged;  if  in  the  deeper  parts,  the  increase  in 
size  is  demonstrated  by  a  flattening  of  the  overlying  convolu- 
tions. In  all  cases  the  necrotic  area  is  characterised  by  its 
soft  consistence,  and  in  most  cases  by  a  change  in  colour  from 
that  of  the  surrounding  parts.  The  amount  of  softening  varies 
with  the  age  of  the  lesion.  When  death  has  ensued  almost 
immediately  upon  the  obliteration  of  a  large  artery,  the  amount 
of  softening  may  be  difficult  to  detect.  A  little  later  the 
tissue,  although  permitting  section,  is  obviously  moist  and 
crumbly.  Within  a  few  days  the  central  parts  of  the  necrosed 
area  may  be  reduced  to  the  consistence  of  creamy  milk.  The 
necrotic  tissue  may  be  white,  red  or  yellow.     The  absence 


no        ISCHAEMIC  SOFTENING  OF  THE  BRAIN 

of  colour  in  the  white  patches  is  due  to  the  ischaemia.  The 
red  tint  is  the  result  of  the  general  capillary  congestion  re- 
sulting from  infarction  and  the  escape  of  blood  from  these  vessels 
by  the  rupture  of  their  walls.  Yellow  softening  is  usually 
of  older  standing,  and  its  colour  depends  on  the  presence  of 
altered  blood  pigment  and  of  the  fatty  products  of  myelin 
disintegration.  Yellow  softening  of  the  surface  convolutions 
is  generally  associated  with  a  diminution  in  their  size.  In 
such  an  area  the  fissures  are  widened,  and  the  leptomeninges 
cannot  be  peeled  from  the  surface  without  disintegration  of 
the  latter. 

Old  softenings  are  often  represented  by  cystic  cavities  which 
may  or  may  not  be  loculated,  and  which  are  filled  with  clear  or 
slightly  turbid  fluid.  In  other  cases,  when  the  destruction  of 
tissue  has  not  been  so  complete,  the  convolutions  may  be 
represented  by  narrow  strips  of  a  substance  resembling  wash- 
leather.  A  still  less  severe  form  of  necrosis  is  represented  by 
convolutions  which  are  somewhat  atrophied,  and  marked  on 
their  surface  by  indentations  giving  an  appearance  similar  to 
that  of  beaten  silver. 

Microscopical  appearances. — In  a  very  recent  case  the  only 
manifestation  of  the  arrested  circulation  may  be  the  coagula- 
tion of  the  blood  in  the  distended  vessels.  Necrosis  of  the 
tissues  follows  rapidly,  and  the  first  evidence  of  this  change  is 
afforded  by  the  altered  reaction  of  the  various  elements  to 
artificial  stains  used  in  the  preparation  of  microscopical 
sections.  When  stained  by  haematoxylin  the  nuclei  are  paler 
than  those  in  healthy  parts.  If  the  Weigert-Pal  method  is 
employed,  the  myelin  substance  fails  to  take  on  the  normal 
dark  blue  coloration,  and  if  Marchi  preparations  are  made,  the 
medullary  sheaths  appear  dark,  swollen  and  partly  pigmented. 
Nerve  cells  in  the  affected  area  may  be  either  swollen  and 
chromolytic  or  shrunken,  broken  and  homogeneously  stained. 
After  the  lapse  of  two  or  three  days  the  whole  appearance  of 
the  softened  part  is  altered.  In  addition  to  the  normal  con- 
stituents of  the  tissues,  there  are  to  be  seen  numbers  of  large 
round  cells  containing  one  or  two  nuclei.  These  are  the  so- 
called  compound  granular  or  fat  granule  cells  which  by  suitable 
methods  may  be  shown  to  contain  numerous  fat  droplets, 
the    products    of    tissue    degeneration.     Their    origin   is    not 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN    iii 


Fig.  27. 

Photographs  of  a  brain  illustrating  the  appearances  produced  by  vascular 
lesions  of  varying  severity.  The  somewhat  battered  aspect  of  some  convolu- 
tions is  the  result  of  moderate  interference  with  the  circulation.  The  poren- 
cephaly in  the  left  post-central  region  indicates  a  considerable  loss  of  tissue. 


112  ISCHAEMIC  SOFTENING  OF  THE  BRAIN 


Fig.  28. 

Softened  cortex  resulting  from  arterial  thrombosis,  showing  granular  corpuscles  and 
necrotic  pyramidal  cells.     (Stained  by  haematoxylin  and  van  Gieson.) 


f 


.*••-%.' 


^••c#^' .-.*'•'■  ••-■•'■■■  :'•■'  ^ 


r  " 


I  \.  * 


»         -.      f      • 


•     #.•!■'•■ 


-  g, 


•^: 


Fig.  29. 

Fat-laden  granular  corpuscles  in  an  area  of  cerebral  softening,  the  result  of 
embolism  of  a  cerebral  artery.     (Haematoxylin  and  van  Gieson.) 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN    113 

absolutely  determined,  but  many  of  them  probably  represent 
the  proliferation  of  neuroglial  cells,  while  others  may  be  derived 
from  fibroblasts.  Whatever  their  derivation  may  be,  they 
act  as  scavengers,  and  may  be  found  chiefly  in  lymphatic 
spaces  around  blood  vessels,  and  in  the  scars  of  all  recent  and 
long-standing  softenings  of  the  central  nervous  system. 

The  fate  of  the  neuroglia  varies  with  the  region  examined. 
In  the  central  parts  of  the  softened  area  the  neuroglia  is 
destroyed  along  with  the  more  specialised  nervous  structures. 


•^ijHk 


Fig.  30. 


Softened  brain  tissue  with  fat-laden  granular  corpuscles  stained  by  the 
Marchi  method. 


but  in  the  peripheral  zones — that  is  to  say,  in  the  parts  where 
the  ischaemia  is  only  relative,  sufficiently  severe  to  bring  about 
necrosis  of  nerve  cells  and  nerve  fibres,  but  insufiicient  to 
destroy  the  more  resistant  supporting  structures — evidence  of 
neuroglial  reaction  is  readily  detected.  The  neuroglial  cells 
are  increased  in  size,  their  processes  are  more  conspicuous 
and  more  numerous,  and  their  nuclei  undergo  division  and 
multiplication.  At  a  somewhat  later  period  the  neuroglial 
fibrils  become  more  and  more  prominent,  and  form  a  dense 
network  to  which  the  term  sclerosis  i»  properly  applied.     From 


114  CIRCULATORY  DISTURBANCES  OF  THE  BRAIN 

each  peripheral  zone  of  neuroghal  activity  the  process  of  repair 
extends  inwards  towards  the  centre  of  the  focus  of  softening, 
and  an  effort  is  made  to  replace  the  nervous  elements  which 
have  disappeared  by  new-formed  glial  tissue.  There  are,  no 
doubt,  small  patches  of  softening  in  which  the  neuroglia  is. 
nowhere  completely  destroyed,  and  in  which  its  reaction  is  so 
early  and  complete  that  the  parts  retain  a  good  deal  of  their 
former  consistence  and  shape,  although  they  have  been  de- 
prived of  their  nervous  constituents.  Such  is  the  case  in  some 
of  the  yellow,  shrunken,  but  fairly  tough,  convolutions  which 
have  been  described  above. 

There  is  another  form  of  scar  tissue  to  which  the  term 
"  lacunar  "  is  applied  owing  to  its  appearance.  It  is  charac- 
terised by  a  number  of  spaces  separated  from  each  other  by 
strips  of  tissue  composed  of  neuroglial  fibres  with  perhaps  a 
few  cells  surrounding  a  thickened  blood  vessel.  These  small 
cavities  contain  a  liquid^in  which  are  to  be  found  drops  of  fat, 
compound  granular  cells,  crystals  derived  from  the  blood 
pigment,  and  particles  of  cholesterin. 

Some  of  the  blood  vessels  within  the  necrosed  area,  which 
no  longer  contain  circulating  blood,  disappear  with  the  other 
tissue  elements.  Others  remain  as  strands  of  connective 
tissue,  with  obliterated  lumen,  to  take  part  in  the  formation  of 
the  scar  tissue.  The  majority,  however,  appear  to  regain  their 
function;  at  any  rate,  in  the  softened  areas,  it  is  usual  to  find 
a  large  number  of  small  vessels  in  which  circulation  is  re- 
established. Newly  formed  vessels  and  fibroblasts  also  appear 
and  gradually  replace  the  products  of  disintegration,  with  the 
result  that  the  margins  of  the  necrosed  area  may  be  largely 
composed  of  young  granulation  tissue. 

The  more  remote  effects  of  the  destruction  of  nervous  tissue 
are  to  be  found  in  the  changes  which  take  place  in  the  affected 
neurons.  For  instance,  a  patch  of  softening  in  the  posterior 
part  of  the  internal  capsule  produces  atrophy  and  disappearance 
of  the  Betz  cells  in  the  corresponding  motor  cortex,  as  well  as 
degeneration  of  the  pyramidal  fibres  throughout  their  course  in 
the  mid-brain,  medulla,  and  spinal  cord.  This  is  a  common  occur- 
rence in  cases  of  hemiplegia.  Similarly,  pontine  thrombosis 
leads  to  secondary  degeneration  of  the  ascending  and  descend- 
ing tracts  passing  through  that  region,     {v.  Figs.  31  and  32.) 


THROMBOSIS  OF  CEREBRAL  ARTERIES         115 


Degeneration  of  the  pyramidal  tract  due  to  softening  of  the  internal  capsule, 
stained  by  the  Marchi  method:  a,  decussation  of  pyramid;  b,  thoracic  cord. 


ii6 


PONTINE  THROMBOSIS 


Fig.  32. 

Fouf  sections  from  a  case  of  pontine  thrombosis  illustrating  the  secondary 
degeneration  in  the  pyramidal  tract:  a,  decussation  of  pyramid;  h,  cervical 
enlargement;  c,  thoracic  region;  d,  lumbo-sacral  enlargement  (Weigert-Pal). 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN    117 

2.  Cerebral  Haemorrhage. 

Haemorrhage  on  the  surface  or  within  the  substance  of  the 
brain  is,  in  the  great  majority  of  instances,  arterial,  and  rarely 
venous,  in  origin.  The  immediate  cause  of  haemorrhage  is 
the  rupture  of  some  artery  which  has  undergone  pathological 
changes,  such  as  arterio-sclerosis  or  atheroma.  In  a  certain 
proportion  of  cases  the  blood  escapes  into  the  tissues 
from  a  miliary  aneurysm,  which  has  resulted  from  hyaline 
degeneration  in  the  vessel  wall.  While  disease  of  the  arterial 
wall  is  the  most  important  factor  in  cerebral  haemorrhage, 
an   associated   rise   in   blood    pressure  and   hypertrophy   of 


Fig.  33. 
Haemorrhage  from  the  anterior  cerebral  artery  ploughing  up  the  frontal  lobe. 

the  left  ventricle  of  the  heart  are  others  which  play  no 
insignificant  part. 

Haemorrhage  may  take  place  from  any  cerebral  artery,  but 
there  are  certain  localities  in  which  the  event  is  more  frequently 
observed  than  in  others.  Haemorrhages  are  more  common 
within  the  brain  substance  than  on  the  surface,  and  they  are 
most  frequent  in  the  central  grey  matter  of  the  basal  ganglia, 
and  especially  in  the  region  of  the  external  capsule  and  lenticular 
nucleus.  In  this  situation  are  found  the  lenticulo-optic  and 
lenticulo-striate  arteries,  and  one  of  the  latter  received  the 
name  of  "  the  artery  of  cerebral  haemorrhage  "  from  Charcot. 

Extravasations  of  blood  may  be  of  any  size  and  any  shape, 


ii8  CIRCULATORY  DISTURBANCES  OF  THE  BRAIN, 

and  they  make  room  for  themselves  partly  by  pressing  back 
and  partly  by  tearing  up  the  substance  of  the  brain.  Cerebral 
haemorrhages  may  be  limited  in  their  extent  or  may  penetrate 
as  far  as  the  lateral  ventricle  on  the  one  side  or  the  surface  of 
the  cortex  on  the  other.  A  ventricular  haemorrhage  is  the 
result  in  one  case  and  a  subarachnoid  extravasation  in  the 
other.  A  ventricular  haemorrhage  may  extend  through  the 
aqueduct  of  Sylvius  and  the  fourth  ventricle  into  the  sub- 
arachnoid cistern  in  the  posterior  fossa  of  the  skull,  whence  the 
blood  may  escape  into  the  spinal  subarachnoid  space,  usually 
tracking  along  the  dorsal  surface  of  the  cord. 

Gross  appearances. — A  large  recent  haemorrhage  into  the 
substance  of  one  hemisphere  may  give  rise  to  obvious  changes 
on  the  surface  of  the  brain.  The  affected  hemisphere  is  more 
voluminous  than  its  fellow,  and  the  convolutions  on  its  surface 
are  flattened  and  sometimes  anaemic.  On  section  the  seat 
of  haemorrhage  is  occupied  by  a  red  clot,  which  is  easily  separ- 
able from  the  adjacent  cerebral  substance.  The  latter  is 
infiltrated  and  discoloured  to  some  extent  by  the  blood,  and 
small  haemorrhages  are  frequently  found  in  the  neighbourhood. 
The  surrounding  tissues  may  also  be  softer  than  normal,  owing 
to  the  presence  of  oedema. 

At  a  later  period  the  clot  and  the  walls  of  the  haemorrhagic 
cavity  are  found  to  have  undergone  certain  changes.  The  clot 
tends  to  shrink,  remaining  red  in  the  centre  and  yellowish  in  its 
peripheral  parts.  At  the  edges  nervous  elements  may  be 
mixed  up  with  crystals  of  blood  pigment  and  the  debris  of 
disintegrated  brain  substance.  After  the  lapse  of  a  certain 
time  the  coagulum  becomes  completely  absorbed,  and  its 
place  may  be  taken  either  by  proliferated  scar  tissue  or  by  a 
quantity  of  more  or  less  blood-stained  fluid. 

While  these  changes  are  going  on  in  the  blood  clot,  there  are 
others  taking  place  in  the  walls  of  the  cavity.  The  latter 
comprise  the  destruction  of  nervous  elements  and  the  pro- 
liferation of  the  neuroglial  tissue.  The  tendency  of  the  new- 
formed  glial  substance  is  either  in  the  direction  of  forming 
a  thin  lining  membrane  to  the  cavity,  or,  in  other  instances, 
towards  the  creation  of  a  network  which  binds  the  walls 
together. 

The  final  results  may  be  either  a  large  single  cavity  con- 


CEREBRAL  HAEMORRHAGE 


119 


Fig.  34- 

Three  photographs  from  a  case  of  cerebral  haemorrhage  with  extravasation  of 
blood  into  the  ventricles  and  minor  haemorrhages  in  the  pons. 


120    ANEURYSMS  OF  THE  CEREBRAL  ARTERIES 

taining  serous  fluid,  a  multilocular  cavity  with  similar  contents, 
or  a  linear  scar  obliterating  the  site  of  the  previous  extrava- 
sation. It  may  be  readily  understood  that  these  relics  of 
haemorrhagic  catastrophes  can  scarcely  be  distinguished  from 
those  of  other  vascular  or  inflammatory  lesions  of  similar 
antiquity. 

Microscopical  changes. — Owing  to  the  presence  of  a  foreign 
body  in  the  form  of  a  blood  clot,  the  neighbouring  brain  matter 
is  rendered  anaemic  and  oedematous.  Consequently  the 
nerve  fibres  and  nerve  cells  undergo  degenerative  changes, 
such  as  have  been  described  under  ischaemic  softening  of  the 
brain  (p.  105).  The  cells  tend  to  become  swollen  and 
chromolytic.  The  medullary  sheaths  of  the  axons  swell  up, 
become  fragmented,  and  undergo  fatty  changes.  The  axis 
cylinders  become  varicose  and  may  break  up  into  short  frag- 
ments. As  early  as  the  second  or  third  day  numerous  com- 
pound granular  cells  appear  on  the  scene,  and  these  take  up  into 
their  interior  detritus  of  all  kinds,  including  fat  droplets  and 
pigment  granules.  Finally,  these  scavenger  cells  wander  into 
the  lymphatic  spaces  of  the  vessel  walls,  and  so  enlarge  the 
meshes  of  their  adventitial  sheaths.  In  the  meantime,  the 
apoplectic  focus  is  invaded  by  young  vascular  sprouts  and 
spindle-shaped  connective-tissue  cells  with  large  vesicular 
nuclei.  These  form  a  granulation  tissue  which  gradually  tends 
to  fill  the  haemorrhagic  cavity.  Simultaneously  the  neuroglial 
tissue  proliferates  and  produces  a  network  of  fibres  which 
shares  in  the  formation  of  the  permanent  scar. 

3.  Aneurysms  of  the  Cerebral  Arteries. 

The  arteries  at  the  base  of  the  brain  may  be  the  seat  of 
aneurysmal  dilatations  which  differ  in  no  way  from  similar 
structures  found  in  the  arterial  system  of  the  body  generally. 
These  do  not  require  any  further  description  here.  On  the 
other  hand,  the  cerebral  arteries  are  sometimes  the  seat  of 
miliary  aneurysms  which  were  first  described  by  Charcot  and 
Bouchard,  who  regarded  them  as  secondary  to  arterio-capillary 
fibrosis.  These  appear  in  the  form  of  small  round  bodies 
about  the  size  of  a  pin's  head,  red  or  greyish-red  in  colour,  and 
either  imbedded  in  the  substance  of  the  brain  or  situated 
on  its  surface      They  may  be  scarce  or  numerous.     They  are 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN     121 

often  difficult  to  detect,  unless,  in  the  case  of  a  recent  haemor- 
rhage, the  affected  region  is  more  or  less  broken  up  in  water, 
so  that  the  brain  substance  separates  from  the  finer  arterial 
and  capillary  vessels  and  enables  the  observer  to  examine  the 
latter  in  detail.  If  this  course  is  adopted,  it  is  customary  to 
find  that  the  vessels  which  are  the  seat  of  one  or  more  aneurysmal 
dilatations  show  marked  sclerotic  changes  in  their  walls.  A 
section  through  the  aneurysm  itself  shows  that  its  wall  consists 
only  of  connective  tissue,  the  muscular  fibres  and  inner  coat 
having  disappeared. 

4.  False  Porencephaly. 

False  porencephaly  (p.  56)  results  from  a  softening  of  the 
brain  due  to  some  vascular  lesion.  In  contradistinction  to 
true  porencephaly  it  has  no  communication  with  the  lateral 
ventricle,  although  there  are  exceptional  cases  with  extensive 
excavation  in  which  this  occurs.  The  wall  of  the  cavity  has 
no  respect  for  the  architecture  of  neighbouring  structures,  and 
convolutions  may  be  half  destroyed  and  cut  across  irregularly. 
The  crater-like  excavation  is  usually  of  considerable  size,  and  its 
walls  may  be  lined  by  a  membrane  formed  partly  of  glial  and 
partly  of  connective  tissue.  It  may  be  traversed  by  bands  of 
similar  structure.  Microscopical  examination  of  the  neigh- 
bouring brain  substance  generally  reveals  a  diminution  in  the 
quantity  of  nervous  elements.  The  fluid  in  the  cavity  may 
contain  remnants  of  brain  substance  and  a  certain  amount  of 
colouring  Tffilfter  derived  from  the  blood.  It  is  not  unusual 
to  find  in  the  brain  which  is  the  seat  of  a  false  porencephaly 
other  patches  of  softening  or  sclerosis.  The  majority  of  these 
cases  result  from  pathological  lesions  occurring  in  early  life, 
and  may  in  some  instances  be  antenatal  in  origin. 

5.  Meningeal  Haemorrhage. 

This  term  may  be  conveniently  applied  to  all  conditions 
under  which  blood  escapes  from  the  intracranial  arteries  or 
veins,  and  accumulates  somewhere  between  the  surface  of  the 
brain  and  the  inner  aspect  of  the  cranium.  The  extravasation 
may  be  either  subarachnoid,  subdural  or  extradural.  Haemor- 
rhages, generally  of  small  dimensions,  in  any  of  these  situations 


122  MENINGEAL  HAEMORRHAGE 

may  be  due  to  certain  obscure  causes,  which  are  embraced 
under  the  term  haemorrhagic  diathesis,  and  which  prevail 
in  purpura,  haemophiha,  pernicious  anaemia,  scurvy,  the 
maUgnant  examples  of  the  acute  specific  fevers,  alcoholism,  etc. 
Such  accidental  complications  of  diseases,  sufficiently  serious 
in  themselves,  have  not  the  same  clinical  importance  as  cases 
of  meningeal  haemorrhage  in  which  a  profuse  escape  of  blood, 
with  its  power  of  irritating  and  compressing  the  brain  tissue, 
is  responsible  for  grave  symptoms.  The  pathology  of  the 
latter  group,  therefore,  must  attract  most  of  our  attention. 

(a)  Subarachnoid  haemorrhage. — Extravasations  of  blood  of 
varying  size  in  the  subarachnoid  space  are  found  in  all  cases 
of  severe  injury  to  the  surface  of  the  brain,  especially  in  bruises 
and  lacerations  resulting  from  blows  on  the  skull,  with  or 
without  fracture  of  the  latter.  The  haemorrhage  is  not  con- 
fined to  that  part  of  the  cerebral  surface  which  corresponds  to 
the  cranial  injury,  but,  through  the  influence  of  "  contrecoup," 
may  be  equally  well  marked  in  distant  regions,  especially  at  the 
opposite  pole. 

Blood  often  finds  its  way  into  the  subarachnoid  space  after 
rupture  of  a  cerebral  artery,  either  in  a  sulcus  or  in  the  substance 
of  the  brain.  In  the  latter  case,  the  blood  forces  its  way  to  the 
surface  through  the  nervous  tissues.  Similarly  an  aneurysm, 
most  frequently  in  the  circle  of  Willis,  may  rupture  into  the 
subarachnoid  space  and  cause  an  extensive  haemorrhage  at 
the  base  of  the  brain.  Such  an  accident  leads  to  a  rapidly 
fatal  issue  in  most  cases,  and  the  extravasated  blood  may  often 
be  traced  through  the  foramen  magnum  and  along  the  surface 
of  the  cord  to  its  lower  extremity. 

(b)  Subdural  haemorrhage. — This  is  usually  the  result  of 
trauma,  and  due  to  the  rupture  of  a  meningeal  artery  or  venous 
sinus.  Haemorrhages  in  this  situation  are  not  uncommon 
in  newly  born  infants,  in  consequence  of  injury  to  the  skull 
and  dura  mater  during  birth.  Such  extravasations  are  found 
on  the  surface  of  one  or  both  cerebral  hemispheres,  and  are, 
according  to  some  observers,  the  cause  of  some  cases  of  infantile 
hemiplegia  or  diplegia.     More  often  they  are  rapidly  fatal. 

In  adults,  a  blow  on  the  skull,  with  or  without  fracture  of 
the  latter,  may  cause  rupture  of  the  superior  longitudinal  sinus 
or  one  of  its  tributaries.     Slow  oozing  of  blood  takes  place, 


PACHYMENINGITIS  HAEMORRHAGICA  INTERNA  123 

and,  accumulating  between  the  dura  and  the  arachnoid 
membranes,  brings  about  gradual  compression  of  one  cerebral 
hemisphere.  Hemiplegia,  hemianaesthesia,  hemianopia,  coma 
and  death  may  follow,  unless  the  condition  is  relieved  by 
operative  interference. 

Arterial  haemorrhage  within  the  subdural  space  may  follow 
severe  injuries  to  the  skull,  and  compression  symptoms  arise 
much  more  rapidly  than  when  the  pressure  is  due  to  venous 
bleeding. 

Pachymeningitis  haemorrhagica  interna  is  a  term  applied  to 
a  somewhat  rare  condition,  found  either  alone  or  in  association 
with  other  morbid  states.  In  a  mild  form  it  is  present  in  a 
few  cases  of  pulmonary,  cardiac  or  renal  disease,  but  more 
frequently  it  accompanies  chronic  brain  affections  with  atrophy 
of  the  convolutions,  such  as  is  met  with  in  general  paralysis  of 
the  insane,  Huntington's  chorea,  and  long-standing  alcoholism. 
The  pathological  appearances  are  characteristic.  On  the  inner 
surface  of  the  dura  there  is  deposited  a  pale  greyish-red  or 
yellowish-red  material,  which,  by  its  laminated  composition, 
suggests  a  series  of  haemorrhages,  some  recent  and  some 
old  and  organised.  The  dura  mater  may  be  thickened  in  some 
cases.  In  others  it  is  of  normal  density  but  tightly  stretched. 
The  haemorrhagic  membrane  may  be  easily  stripped  off  the 
surface  of  the  brain,  or  may  be  firmly  adherent  to  the  arachnoid 
membrane.  The  condition  may  be  limited  to  the  outer 
aspect  of  one  hemisphere,  or  it  may  affect  both,  and  even  in 
exceptional  cases  extend  to  the  base  of  the  brain.  According 
to  some  authorities  the  condition  is  primarily  haemor- 
rhagic, according  to  others,  primarily  inflammatory  in  origin, 
but  its  exact  pathogenesis  is  little  understood.  Microscopical 
examination  reveals  the  presence  of  new  fibrous  tissue  and 
new  blood  vessels,  as  well  as  the  remnants  of  old  haemorrhages 
in  the  form  of  pigment  composed  of  haematoidin  and 
haemosiderin. 

{c)  Extradural  haemorrhage  is  nearly  always  the  result  of  an 
injury  to  the  bones  of  the  skull.  Although  usually  ascribed  to 
rupture  of  one  of  the  branches  of  the  meningeal  arteries,  it  is 
probable,  according  to  the  observations  of  Wood-Jones,  that 
the  bleeding  is  of  venous  origin  in  many  if  not  the  majority 
of  cases.     The  arteries  are  lodged  in  thin-walled  venous  sinuses. 


124       EXTRADURAL  HAEMORRHAGE 

which  are  much  more  easily  damaged  than  the  former.  The 
blood  collects  between  the  dura  mater  and  the  cranium,  and 
by  so  doing  produces  a  haematoma  which,  playing  the  part 
of  a  foreign  body,  compresses  the  subjacent  brain  tissue.  It 
should  not  be  forgotten  that  a  severe  injury  may  produce  at 
once  an  extradural  and  a  subdural  haemorrhage,  as  well  as 
bruising  and  laceration  of  the  brain. 

The  results  of  intracranial  haemorrhage,  whether  extra- 
dural, subdural  or  subarachnoid,  in  cases  which  survive  and 
in  which  measures  are  not  taken  to  remove  the  clot,  are  very 
similar.  The  coagulum  is  partly  absorbed  and  partly  organised 
so  that  scar  tissue,  with  or  without  the  presence  of  cysts, 
forms  the  permanent  remains. 

6.  Sinus  Thrombosis. 

Thrombosis  of  the  cerebral  veins  is  a  rare  event  compared 
to  thrombosis  of  the  cerebral  arteries.  Two  varieties  are 
usually  described:  (i)  primary  or  marantic  sinus  thrombosis; 
(2)  secondary  infective  or  phlebitic  sinus  thrombosis. 

Primary  sinus  thrombosis  is  due  to  diminished  blood  pressure, 
to  changes  in  the  quality,  and  especially  in  the  coagulability, 
of  the  blood  or  to  a  combination  of  these  factors.  It  may  be 
favoured  in  some  instances  by  fatty  degeneration  of  the 
endothelial  lining  of  the  veins  and  their  trabeculae.  It  occurs 
chiefly  in  infancy  and  old  age,  especially  when  the  victim  has 
been  greatly  weakened  by  diarrhoea,  pulmonary  tuberculosis 
or  malignant  disease.  ^  Occasionally  it  is  met  with  in  the  course 
of  one  of  the  acute  specific  fevers,  such  as  typhoid  variola  or 
pneumonia,  but  in  such  cases  some  phlebitis  may  play  an 
important  part.  Severe  cases  of  chlorosis  have  also  been 
reported  in  which  sinus  thrombosis  has  been  a  serious 
complication. 

The  thrombosis  may  be  general  or  confined  to  one  or  two 
sinuses ;  in  the  latter  case,  the  superior  longitudinal  and  the 
lateral  sinuses  are  those  most  commonly  affected.  In  recent 
cases  the  clot  is  of  a  dark  greyish-red  colour.  The  longer  it 
remains  the  paler  is  its  colour  and  the  firmer  is  its  adherence 
to  the  venous  wall. 

The  coagulum  usually  extends  into  the  contributory  veins, 
and  when  the  longitudinal  sinus  is  the  seat  of  the  thrombosis. 


SINUS   THROMBOSIS  125 

the  veins  of  the  cerebral  convexity  are  converted  into  firm,  dark 
purpHsh  tubes.  In  contrast  to  these  clotted  vessels  are  the 
distended  tortuous  veins  containing  fluid  blood.  The  brain 
tissue  from  which  the  thrombosed  vessels  draw  their  blood 
supply  is  usually  oedematous,  congested,  and  perhaps  haemor- 
rhagic  and  softened. 

Secondary  sinus  thrombosis  is  the  result  of  some  inflammatory 
process  involving  the  cranial  bones,  the  cranial  contents  or  the 
tissues  and  cavities  on  the  external  surface  of  the  skull.  Otitis 
media,  necrosis  of  the  temporal  bone  and  suppuration  in  the 
nasal  cavities,  must  be  regarded  as  the  commonest  causes  of 
this  variety,  and  the  otitic  cases  form  the  large  majority. 
Consequently  the  lateral  sinus  is  the  favourite  seat  of  trouble. 
From  it  the  internal  jugular  vein  is  frequently  infected.  Caries 
of  the  cranial  bones,  meningitis,  facial  erysipelas,  orbital 
suppuration,  septic  wounds  of  the  scalp,  and  even  carbuncles 
and  parotitis,  may  be  the  cause  of  phlebitic  sinus  thrombosis. 
Purulent  meningitis,  cerebral  or  cerebellar  abscesses,  and 
general  pyaemia  are  the  most  frequent  complications. 

The  wall  of  the  sinus  is  greenish-yellow  in  colour,  and  the 
clot  within  has  a  dirty  greyish-red  appearance  and  necrotic 
or  purulent  characters.  Suppuration  may  extend  into  the 
layers  of  the  dura  mater  or  to  its  internal  surface.  Secondary 
abscesses,  especially  in  the  lungs,  are  not  uncommon. 

7.  Haematomyelia. 

Although'^haemorrhages  are  found  not  infrequently  in  the 
spinal  cord  of  patients  who  have  suffered  from  acute  inflam- 
matory or  acute  vascular  conditions  of  that  organ,  and  are 
quite  common  in  patients  who  have  died  with  urgent  dyspnoea, 
the  term  haematomyelia  is  generally  reserved  for  cases  in 
which  a  haemorrhage  is  mainly  responsible  for  the  clinical 
symptoms.  Although  cerebral  haemorrhage  is  chiefly  deter- 
mined by  sclerotic  changes  in  the  cerebral  vessels,  the  aetiology 
of  spinal  haemorrhage  appears  to  be  of  an  entirely  different 
nature.  Sclerotic  degeneration  of  spinal  arteries  is  by  no 
means  uncommon,  but  the  rarity  of  haematomyelia,  and  the 
fact  that  it  is  not  by  any  means  clearly  associated  with  arterial 
changes,  is  sufficient  evidence  that  we  must  look  elsewhere  for 
its  principal  cause.     This  is  not  far  to  seek,  as  haematomyelia 


126  HAEMATOMYELIA 

nearly  always  follows  upon  some  definite  injury  affecting  the 
spinal  column.  It  is  associated  frequently  with  fracture- 
dislocation,  but  may  also  arise  when  there  has  been  no  such 
result  of  the  injury.  Blows  upon  the  spinal  column,  falls 
on  the  head  or  the  feet  or  the  sacral  region,  are  the  common 
immediate  precursors  of  the  condition.  Obstetrical  injuries 
have  also  resulted  in  haemorrhage  into  the  child's  spinal  cord. 
Excessive  and  constant  muscular  exertion  is  probably  respon- 
sible in  some  instances,  and  such  conditions  as  haemophilia, 
congenital  or  acquired  fragility  of  the  blood  vessels  and  purpura, 
may  sometimes  be  regarded  as  predisposing  factors.  Haemato- 
myelia  may  occur  at  any  age,  but  is  most  common  between 
those  of  twenty  and  forty,  the  period  of  greatest  physical 
exertion  and  exposure  to  injury.  As  might  be  expected,  men 
are  more  liable  than  women  to  the  condition. 
■  Pathogenesis. — The  grey  matter  of  the  spinal  cord  is  much 
richer  in  vessels  than  the  white  matter,  and  the  tissue  being  of 
a  looser  character  affords  less  support  to  the  vessel  walls.  This 
appears  to  explain  the  common  incidence  of  haemorrhage  into 
the  central  grey  matter,  and  also  the  tendency  for  the  blood 
to  track  its  way  in  a  longitudinal  direction,  that  is  to  say,  in 
the  path  of  least  resistance. 

Morbid  anatomy. — In  recent  cases  nothing  may  be  detected 
on  the  surface  of  the  cord  and  its  meninges,  although  the 
latter  may  present  evidence  of  bruising.  Palpation  with  the 
finger  often  detects  a  soft  fluctuating  swelling,  and  the  eye 
may  sometimes  be  attracted  to  the  dark  bluish-red  hue  of  the 
central  blood  clot,  visible  through  the  surrounding  white 
matter.  The  most  common  site  of  the  haemorrhage  is  in  the 
cervico-thoracic  enlargement ;  its  occurrence  in  the  thoracic  or 
lumbo-sacral  region  is  comparatively  rare.  A  series  of  trans- 
verse sections  shows  that  the  extravasation  may  be  limited  to 
one  or  two  segments  when  it  is  round  or  oval  in  shape,  or  it 
may  extend  through  many  segments  in  the  form  of  tapering 
prolongations  upwards  and  downwards,  in  which  case  it  has 
a  more  spindle-shaped  contour.  The  blood  is  limited  to  the 
grey  matter  at  most  levels,  although  at  the  site  of  the  original 
leakage  the  white  matter  may  be  seriously  encroached  upon. 
The  track  pursued  by  the  haemorrhage  usually  involves  the 
bases  of  the  dorsal  horns,  but  extends  also  in  some  regions 


HAEMATORRHACHIS  127 

into  the  ventral  and  lateral  grey  substance.  Multiple 
haemorrhagic  foci  are  fairly  common.  The  colour  depends 
on  the  age  of  the  haemorrhage,  being  red  in  the  early  cases  and 
brown  or  deep  yellow  in  those  of  longer  standing.  In  very 
old  cases  the  track  of  the  extravasation  may  be  represented 
by  a  kind  of  cyst  containing  clear  fluid,  or  by  narrow  cracks 
or  fissures  with  fairly  well-defined  walls.  Under  the  microscope 
the  substance  of  the  cord  is  seen  to  be  partially  disintegrated 
around  the  blood  clot,  and  is  often  somewlmt  oedematous. 
In  cases  of  a  few  days'  standing,  evidence  of  neuroglial  pro- 
liferation is  usually  observed,  and  large  granular  cells  may  be 
seen  in  considerable  numbers.  In  later  cases  these  changes 
are  replaced  by  the  appearance  of  neuroglial  sclerosis  which 
has  arisen  in  the  process  of  repair.  Secondary  changes  in  the 
nervous  elements  comprise  disappearance  or  atrophy  of  the 
ventral  and  dorsal  horn  cells,  degenerations  in  the  ascending 
or  descending  spinal  tracts,  and  atrophy  of  the  ventral  root 
fibres. 

Relationship  of  anatomical  to  clinical  phenomena. — The 
common  clinical  picture  of  haematomyelia  is  that  presented 
by  a  man  who  has  received  a  serious  injury  to  the  cervical  cord. 
The  origin  of  the  haemorrhage  into  the  grey  matter  of  the 
cervical  enlargement  and  the  consequent  destruction  of  ventral 
horn  cells  is  responsible  for  the  atrophic  palsy  usually  found 
in  the  muscles  of  the  arms  and  hands.  At  the  same  time 
pressure  is  exerted  upon  the  pyramidal  tracts,  which  may  be 
actually  invaded  by  the  extravasation,  with  the  result  that 
the  lower  extremities  are  affected  by  a  spastic  paraplegia. 
The  characteristic  dissociative  anaesthesia  is  brought  about  by 
the  incidence  of  haemorrhage  upon  the  central  parts  of  the 
cord,  whereby  the  fibres  carrying  painful  and  thermal  impulses 
are  involved  as  they  cross  from  one  side  to  the  other.  The 
oculo-pupillary  symptoms  so  oftien  observed  in  these  cases 
are  the  natural  consequence  of  the  involvement  of  the  eighth 
cervical  and  first  thoracic  segments  in  the  morbid  process. 

8.  Haematorrhachis. 

This  somewhat  inelegant  term  is  applied  to  conditions  in 
which  blood  is  found  extravasated  within  the  vertebral  canal. 
It  embraces  at  least  two  or  three  different  types  of  haemor- 


128  HAEMATORRHACHIS 

rhage.  Haemorrhage  between  the  dura  mater  and  the  bony 
walls  of  the  vertebral  canal  or  extrameningeal  haemorrhage 
is  usually  the  result  of  some  injury  to  the  spinal  column  with 
or  without  definite  fracture  or  dislocation.  It  may  also  be 
brought  about  by  the  rupture  of  an  aneurysm  into  that  space, 
and  more  rarely  may  be  produced  as  the  result  of  severe  con- 
vulsive attacks  in  patients  dying  from  eclampsia,  tetanus 
or  the  status  epilepticus.  Diseases  of  the  heart  or  lungs  in 
which  there  is  generally  congestion  of  the  venous  system  may 
have  a  predisposing  influence. 

Subdural  or  intrameningeal  haemorrhage  may  also  result 
from  injury  either  to  the  spinal  column  or  to  the  head.  In  the 
latter  case,  blood  which  is  extravasated  into  the  posterior 
fossa  readily  finds  its  way  into  the  spinal  subdural  space. 
Obstetric  injuries  are  well  recognised  as  a  cause  of  haemorrhage 
in  this  situation,  and  the  convulsive  affections  which  have  just 
been  mentioned  in  connection  with  extradural  haemorrhage 
may  have  their  influence  in  bringing  about  the  intrameningeal 
form.  Similar  haemorrhages  are  common  enough  in  associa- 
tion with  the  haemorrhagic  forms  of  infective  fever,  and  also 
in  connection  with  various  types  of  meningitis,  both  before 
and  at  the  same  time  as  the  serous  or  purulent  exudations 
become  prominent  features. 

Morbid  anatomy. — The  extradural  space  contains  a  large 
number  of  veins  separated  by  a  loose,  fatty  connective  tissue, 
and  the  usual  supine  position  of  the  body  allows  these  vessels 
to  become  easily  engorged.  Post-mortem  haemorrhages, 
therefore,  are  not  uncommonly  produced  in  the  process  of 
exposing  the  spinal  cord,  and  these  must  not  be  confused  with 
extradural  extravasations  originating  during  life.  It  is  very 
rarely  that  haemorrhage  in  this  situation  is  sufficiently  extensive 
to  cause  pressure  upon  the  spinal  cord.  The  opportunities  for 
escape  upwards  and  downwards  are  plentiful,  and  in  large 
extravasations  the  blood  may  even  be  found  extending  along 
the  course  of  the  spinal  nerves  through  the  intervertebral 
foramina. 

An  intrameningeal  haemorrhage  of  greater  or  less  degree  is 
much  more  common  than  the  extradural  variety.  It  is  by  no 
means  uncommon  to  find  the  greater  part  of  the  subarachnoid 
space  throughout  the  length  of  the  spinal  cord  more  or  less 


CIRCULATORY  DISTURBANCES  OF  THE  BRAIN     129 

filled  with  blood  which  has  found  its  way  from  the  cranial 
cavity.  Sometimes,  but  much  more  uncommonly,  a  sub- 
arachnoid haemorrhage  in  the  spinal  canal  may  extend  up- 
wards and  reach  the  ventricles  of  the  brain.  Intrameningeal 
haemorrhage  rarely,  if  ever,  produces  compression  of  the  spinal 
cord,  but,  of  course,  it  is  often  the  result  of  a  trauma  which 
has  also  severely  injured  the  latter  organ.  This  is  a  point 
worthy  of  remembrance  in  connection  with  clinical  work, 
because  operations  performed  light-heartedly  with  a  view  to 
remove  pressure  by  blood  clot  on  the  spinal  cord  after  injuries 
to  the  vertebral  column  may  not  afford  the  relief  of  symptoms 
which  was  expected.  The  symptoms  of  a  transverse  lesion 
of  the  cord  after  spinal  injuries  are  in  the  great  majority 
of  cases  due  either  to  intramedullary  haemorrhage,  to  actual 
laceration  of  the  spinal  tissues  or  to  pressure  exerted  by  dis- 
placed bone,  and  are  not  the  result  of  accumulated  blood  clot 
within  the  dura  mater. 

REFERENCES 

Batten,  F.  E.  :  Haematomyelia.     Allbutt  and  Rolleston,  System  of  Medicine, 

vol.  vii.,  1910,  p.  680. 
Fearnsides,  E.  G.  :  Intracranial  Aneurysms.     Brain,  1914,  vol.  xxxix.,  p.  224. 
Russell,  J.  S.  Risien:  Haematorrhachis.     Allbutt  and  Rolleston,  System  of 

Medicine,  vol.  vii.,  1910,  p.  587. 
Taylor,   James  :   Thrombosis  of  Cerebral  Vessels.     Allbutt  and  Rolleston. 

System  of  Medicine,  vol.  viii.,  1910,  p.  290. 
Wood- Jones,  F.:  The  Vascular  Lesion  in  Middle  Meningeal  Haemorrhage. 

Lancet,  1912,  vol.  ii.,  p.  7, 


CHAPTER  V 

SYPHILIS  OF  THE  NERVOUS  SYSTEM 

The  discovery  by  Schaudinn  of  the  specific  micro-organism  of 
syphilis,  the  Spirochaeta  pallida,  inaugurated  a  new  era  in  our 
knowledge  of  the  pathology  of  syphilis  of  the  nervous  system. 
To  Metchnikoff  and  Roux  we  owe  the  additional  knowledge 
derived  from  observations  on  the  successful  inoculation  of 
animals  with  the  syphilitic  virus,  and  to  Wassermann  we  are 
indebted  for  the  invention  of  his  invaluable,  if  empirical,  test. 
The  interval  which  elapses  between  the  appearance  of  a 
primary  chancre  and  the  onset  of  symptoms  suggesting  cerebro- 
spinal syphilis  is  very  variable.  Headache  is  not  uncommonly 
associated  with  the  constitutional  disturbances  and  cutaneous 
rashes  of  the  secondary  period,  and  it  has  been  shown  that  even 
at  this  time  the  cerebro-spinal  fluid  may  contain  the  virus. 
A  monkey  has  been  successfully  inoculated  with  syphilis 
from  the  cerebro-spinal  fluid  of  a  man  suffering  from  a  papular 
syphilide,  and  spirochaetes  have  been  demonstrated  in  the 
fluid  under  similar  conditions.  The  more  notorious  evidences 
of  nervous  syphilis  are  usually  delayed  for  a  year  or  more  after 
infection.  They  may  appear  within  a  month,  are  fairly 
common  in  the  first,  and  most  frequent  in  the  third  or  fourth 
years.  On  the  other  hand,  ten,  fifteen  or  even  twenty  years 
may  elapse  before  the  nervous  system  exhibits  signs  of  being 
implicated.  Although  it  is  much  more  difficult  to  detect 
spirochaetes  in  the  later  manifestations  of  syphilis  than  in 
earlier  lesions,  it  is  interesting  to  remember  that  an  ape  has 
been  successfully  inoculated  from  a  human  gumma  appearing 
three  and  a  half  years  after  infection.  It  is  further  of  im- 
portance to  remember  that  the  cerebro-spinal  fluid  may  give 
a  positive  Wassermann  reaction  in  the  absence  of  any  evidence 
pointing  to  syphilis  of  the  brain  or  spinal  cord.     There  is  reason 

to  suppose  that  the  virus  of  syphilis  may  lie  latent  in  the 

130 


SYPHILIS  OF  THE  NERVOUS  SYSTEM 


^31 


lymphatic  organs  of  the  body  and  that,  in  the  majority  of 
instances,  attacks  on  the  central  nervous  system  are  delivered 
via  lymphatic  routes. 

Although  the  morbid  tissue  changes  of  a  primary  sore  are 
practically  identical  with  those  of  a  gumma,  the  spirochaete 
is  rarely  demonstrated  in  the  latter  lesion.  This  may  possibly 
be  explained  by  one  or  other  of  the  following  assumptions, 
(i)  Atypical  forms  of  the  spirochaete  remain  latent  in  the 
lymphatic  system  and,  when  the  opportunity  arises,  attack 


Fig.  35. 

Section  of  optic  nerve  in  secondary  syphilis,  showing  enormous  infiltration  of 
Virchow-Robin  space  with  mononuclear  cells,  and  glial  overgrowth  in  the  optic 


some  part  of  the  nervous  system  where  resistance  is  lowered. 

(2)  Atypical  forms  of  the  spirochaete  may  be  lodged  in  the 
nervous  system  and  are  only  roused  into  activity  by  changes 
in  the  surrounding  tissues,  such  as  those  produced  by  injury. 

(3)  One  race  only  of  spirochaete  has  a  special  predilection  for 
multiplication  and  activity  in  nervous  tissues. 

The  essential  lesion  of  syphilis  in  the  nervous  system  may  be 
described  as  a  more  or  less  limited  perivascular  lymphangitis. 
It  is,  therefore,  not  a  disease  of  nervous  tissue  proper,  but  an 
inflammatory  process  which  may  affect  the  nervous  elements 


132 


SYPHILIS  OF  THE  NERVOUS  SYSTEM 


either  by  direct  pressure  and  encroachment,  by  interfering  with 
their  supply  of  nutrition  or  by  poisoning  the  fluids  on  which 
they  depend  for  nourishment.  Although  it  is  convenient 
to  describe  several  varieties  of  lesion  in  connection  with 
syphilis  of  the  nervous  system,  the  microscopical  characters 
of  each  are  virtually  the  same.  Such  differences  as  exist 
depend  probably  upon  degrees  of  virulence,  degrees  of  resist- 
ance, and  purely  anatomical  differences  in  the  locality  of  the 


Fig.  36. 

Drawing  of  a  section  of  the  lumbar  enlargement,  showing  an  intramedullary 
gumma  undergoing  central  caseation. 

initial  infection.  The  perivascular  lymphangitis  is  an  in- 
flammatory process  characterised  by  a  tendency  to  "  gumma- 
tosity."  The  more  active  and  virulent  the  inflammation  the 
less  productive  of  gummatous  tissue ;  the  slower  and  quieter  the 
inflammation  the  more  likely  is  the  formation  of  circumscribed 
gummata. 

We  may  interpret  the  microscopical  features  in  the  following 
way.  The  virus  multiplies  in  the  perivascular  lymph  spaces 
and  incites  a  proliferative  hyperplasia  of  neighbouring  cells, 
endothelial,  conjunctival  and  perhaps  epithelial.     The  result 


GUMMATA  133 

is  an  abundant  mass  of  cells  chiefly  of  the  plasma-cell  and 
lymphocytic  type  filling  the  interstices  of  the  connective  tissue. 
The  proliferative  process  spreads  along  adjacent  lymphatic 
channels,  fresh  cellular  masses  are  added  in  succession,  until 
the  early  and  more  central  parts  of  the  newly-formed  substance 
suffer  from  deficiency  of  nutrition.  Depending  upon  this 
cutting  off  of  nutrient  supplies,  the  central  parts  become  either 
necrotic  or  fibrotic,  frequently  a  mixture  of  both.  The  mass 
is  now  caseous  or  fibrous,  generally  caseous  in  one  part  and 
fibrotic  in  another.  If  the  tendency  to  spread  dies  out  or  is 
combated  by  local  resistance  or  treatment,  the  fibrous  process 
preponderates  in  the  peripheral  parts  in  such  a  way  as  to 
produce  a  tough  wall  around  the  granuloma.  Under  other 
circumstances  the  inflammatory  reaction  tends  to  diffuse 
much  more  rapidly  and  widely,  with  the  result  that  the  forma- 
tion of  gummata  is  less  prominent,  at  any  rate  to  the  naked  eye. 
A  richly  cellular  and  vascular  granulation  tissue  is  then  formed 
with  widespread  adhesions  to  neighbouring  structures. 

With  this  description  of  the  fundamental  change  occurring 
in  syphilitic  inflammation  to  help  us,  we  may  consider  the  three 
varieties  into  which  these  lesions  are  conveniently  divided. 
At  the  same  time,  it  must  not  be  understood  that  these  varieties 
usually  occur  singly ;  on  the  contrary,  it  is  the  rule  to  find  two 
or  more  present  in  every  case  of  cerebro-spinal  syphilis. 

I.  Gummata. — These  gummata,  or  syphilomata,  are  more 
often  multiple  than  single,  and  may  be  found  almost  anywhere 
in  relation  to  the  brain  or  spinal  cord,  although  always  con- 
nected in  some  way  with  the  meninges.  On  the  convexity 
of  the  brain  they  may  spring  from  the  dura  mater  or  the 
leptomeninges  and,  when  deep-seated,  arise  from  the  pial 
trabeculae  which  penetrate  between  the  convolutions  and 
follow  the  course  of  the  vessels.  At  the  base  of  the  brain 
and  in  the  spinal  cord  they  usually  originate  from  the  pia- 
arachnoid,  and  the  same  may  be  said  of  those  which  are  found 
on  the  cranial  nerves  or  the  spinal  roots.  Their  size  is  ex- 
tremely variable  and  their  shape  irregularly  spherical,  often 
with  nodular  projections.  The  main  colour  is  greyish  or 
greenish-yellow,  but  the  circumference  is  often  tinged  with 
pink  owing  to  its  greater  vascularity.  The  consistence  varies 
with  the  relative  amount  of  tough  fibrous  tissue   and  soft 


134 


SYPHILIS  OF  THE  NERVOUS  SYSTEM 


Fig.  37. 

Two  sections  through  the  brain  of  a  patient  with  extensive  gummatous  menin- 
gitis and  meningo-encephaWis.  This  process  was  fairly  general  over  the  surface 
of  both  hemispheres,  but  was  most  advanced  in  the  right  fronto-parietal  region. 


GUMMATOUS  MENINGITIS  135 

necrotic  material.  They  may  be  definitely  encapsulated,  but 
the  capsule  is  always  more  or  less  adherent  to  adjacent  tissues. 
Under  the  microscope  the  peripheral  parts  of  the  gumma  are 
seen  to  be  richly  cellular,  and  sometimes  to  contain  numerous 
new  vessels.  The  cells  are  chiefly  of  the  plasma  and  lympho- 
cytic type,  but  spindle  and  stellate  cells  of  connective-tissue 
origin  may  be  abundant.  In  the  more  central  zones  there  is 
often  much  amorphous  material  which  represents  the  necrosed 
cells  and  which  may  contain  fatty  globules.     Bands  of  fibrous 


:,  : . : '  ■  vfv':- ••,•.:'.  ■'.■ft.,---  ■:■;  «?..•«„■«■  /i-nA--: .  •.^-■:''* 


Fig.  38. 

A  section  from   sclerosed   area  of  brain  underlying  the  gummatous  meningitis 
shown  in  Fig.  37,  and  showing  proliferation  and  enlargement  of  neuroglial  cells. 

tissue  divide  the  masses  of  caseous  substance.  Around  the 
gumma  there  is  often  an  area  of  meningitis  on  the  one  hand,  and 
encephalitis  or  myelitis  on  the  other.  In  addition,  the  effect 
of  pressure  on  the  adjacent  tissue  may  be  observed  in  the  form 
of  oedema,  neuroglial  proliferation  or  softening  and  rarefaction. 
2 .  Gummatous  meningitis. — Syphilitic  meningitis  may  involve 
the  hard  and  soft  membranes  together,  and  occasionally  the  soft 
membranes  alone.  The  best  examples  of  pachymeningitis, 
i.e.  inflammation  of  the  dura  and  pia-arachnoid,  are  seen  on 
the  convexity  of  the  hemispheres  and  in  the  cervical  region  of 


136  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

the  cord.  The  whole  of  one  or  both  hemispheres  may  be  covered 
with  a  dense  adherent  membrane  as  much  as  an  eighth  of  an 
inch  thick.  A  similar  tough  sheath  may  tightly  embrace 
considerable  areas  of  the  spinal  cord,  and  lead  to  softening 
of  the  latter  by  interference  with  its  blood  supply  and  by  direct 
pressure  on  its  substance. 

Leptomeningitis,  with  no  involvement  of  the  dura,  is  ex- 
ceedingly common  at  the  base  of  the  brain  and  over  the  lower 
parts  of  the  spinal  cord,  although  in  the  latter  situation  the 
theca  is  generally  adherent  to  the  inflamed  pia-arachnoid. 
The  interpeduncular  space  and  optic  chiasma  is  perhaps 
the  most  frequent  site  of  gummatous  meningitis,  and  in  this 
situation  may  involve  the  third  nerves  and  also  the  various 
branches  of  the  circle  of  Willis.  Remote  effects  on  the  cerebral 
circulation  may  be  produced  in  the  latter  case.  Both  in  the 
brain  and  spinal  cord  the  meningitis  is  always  associated 
with  more  or  less  inflammation  of  the  subjacent  nervous  tissue. 
Sections  of  the  latter  show  infiltration  of  the  perivascular 
sheaths  with  lymphocytes  and  plasma  cells,  thickening  of  the 
pial  trabeculae,  and  sometimes  neuroglial  hyperplasia.  Nerve 
cells  and  fibres  near  the  surface  are  often  observed  in  various 
stages  of  disintegration. 

An  interesting  secondary  result  of  basal  meningitis  in  the 
posterior  fossa  of  the  skull  is  found  occasionally  in  the  form 
of  an  hydrocephalus,  due  to  the  blocking  of  the  posterior  outlet 
of  the  fourth  ventricle.  This  occurs  in  adults  as  well  as 
children,  although  the  cranial  deformities  are  not  so  prominent 
in  the  former  and  the  fatal  issue  is  much  more  speedy. 

The  microscopical  appearances  of  gummatous  meningitis 
can  be  readily  inferred  from  what  has  been  already  stated. 
The  meninges  are  densely  infiltrated  with  cells,  and  scattered 
about  are  nodules  which  may  be  caseous  or  fibrotic.  There  is 
always  a  certain  amount  of  arteritis  and  phlebitis,  often  leading 
to  great  thickening  of  the  vessel  walls  and  sometimes  to  oblitera- 
tion of  their  lumina. 

Pachymeningitis  cervicalis  hypertrophica  consists  of  a  primary 
thickening  of  the  dura  mater  in  the  cervical  region  of  the 
spine,  leading  to  secondary  changes  in  the  spinal  cord  and 
nerve  roots.  The  majority  of  cases  undoubtedly  owe  their 
origin  to  syphilis.     Whether  this  is  a  constant  aetiological 


PACHYMENINGITIS  CERVICALIS  137 

factor  or  not  will  probably  be  settled  in  the  course  of  the  next 
few  years,  when  it  will  be  possible  to  correlate  the  results  of 
the  serological  examination  of  a  number  of  cases  of  this  some- 
what rare  condition.  In  a  considerable  proportion  of  the 
cases  described  the  symptoms  have  commenced  after  a  trauma 
to  the  spine,  or  after  some  infectious  disease.  Some  of  the 
slighter  cases  appear  to  be  attributable  to  chronic  alcoholism. 

On  removal  of  the  cord  in  its  envelopes  from  the  spinal  canal, 
the  cervical  region  is  seen  to  be  swollen  in  an  elongated  spindle, 
and  to  be  extremely  firm  and  hard.  The  swollen  cord  may 
completely  fill  the  spinal  canal,  and  may  be  abnormally  ad- 
herent to  the  posterior  common  ligament  of  the  vertebrae. 
Apart  from  that,  the  outer  surface  of  the  dura  mater  shows 
little  abnormality.  The  nerve  roots  may  show  evidence  of 
atrophy  due  to  pressure,  but  are  often  apparently  normal. 
It  is  extremely  difficult,  and  often  impossible,  to  separate  the 
thickened  dura  mater  from  the  pia-arachnoid  to  which  it  is 
closely  adherent ;  and  the  cord  is  thus  enveloped  by  a  compact 
fibrous  ring,  which  may  obliterate  all  trace  of  a  subarachnoid 
space.  Calcareous  plaques  are  often  present  in  this  dense 
fibrous  tissue.  Some  thickening  of  the  pia-arachnoid  is  also 
usually  present. 

The  cord  itself  is  more  or  less  sclerosed,  but  sometimes  it  is 
swollen  and  oedematous.  Very  often  it  contains  a  central 
cavity  which  appears  to  be  due  to  the  constriction  of  its  nutrient 
blood  vessels  by  the  thickened  membranes.  This  extends  for 
a  greater  or  less  distance  up  and  down  the  cord  from  the  seat 
of  the  lesion.  Along  with  this  there  is  some  degeneration  in 
the  longer  ascending  and  descending  tracts.  An  analogous 
process  is  sometimes  found  at  the  base  of  the  brain,  and  may  be 
continuous  with  the  disease  in  the  cervical  region. 

The  controversy  which  existed  for  many  years  as  to  whether 
the  thickening  of  the  membranes  was  primary  or  secondary 
to  a  condition  of  syringomyelia  may  now  be  considered  settled. 
There  is  no  doubt  that  constriction  of  the  vessels  supplying  the 
cord  may  produce  a  central  cavitation  which  may  extend  a 
considerable  distance  from  the  lesion.  For  this  reason  it  is 
often  difficult  clinically  to  distinguish  between  primary 
syringomyelia  and  pachymeningitis  cervicalis  hypertrophica. 
The  root  pains,  anaesthesia,  and  muscular  atrophy  are  due 


138  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

partly  to  direct  nipping  of  the  nerve  roots  in  their  passage 
through  the  thickened  dura  mater,  and  partly  also  to  the 
diminished  blood  supply  to  the  grey  matter  of  the  cord. 

3.  Gummatous  arteritis. — It  is  an  almost  invariable  rule  that 
cases  of  cerebro-spinal  syphilis  show  more  or  less  arterial  change, 
in  the  form  of  thickening  of  the  vessel  walls,  even  when  the 
most  prominent  lesions  are  circumscribed  gummata  or  patches 
of  meningitis.  This  obtains  not  only  with  regard  to  the 
arteries  in  the  immediate  neighbourhood  of  the  gummatous 
lesion,  but  to  many  of  the  vessels  throughout  the  central 
nervous  system.  On  the  other  hand,  there  are  cases  in  which 
the  chief  brunt  of  the  disease  falls  on  the  arteries,  with  the 
result  that  aneurysms,  haemorrhages  and  thromboses  play 
the  principal  part  in  the  production  of  symptoms.  Syphilitic 
arteritis  may  affect  vessels  in  either  a  diffuse  or  nodular  manner, 
the  affected  parts  being  rigid,  thickened,  and  of  a  yellow  or 
greenish-yellow  colour.  The  arteries  composing  the  circle  of 
Willis  are  a  favourite  site  for  these  changes,  but  vessels  of  much 
smaller  calibre  may  be  equally  involved. 

Much  controversy  has  arisen  concerning  the  exact  course 
of  the  pathological  changes  in  this  form  of  arteritis.  Into 
the  details  of  this  we  will  not  enter,  but  will  adopt  the  view 
of  Mott,  which  is  most  in  accord  with  our  own  experience. 
The  virus  attacks  the  vessel  from  its  outer  aspect — that  is  to 
say,  it  initiates  active  changes  in  the  lymphatic  spaces  of  the 
adventitial  sheath,  and  so  starts  a  gummatous  process  identical 
with  that  which  we  have  already  described  in  connection  with 
the  meninges.  The  result  of  this  change  is  to  interfere  with 
the  vasa  vasorum,  and  so  with  the  circulation  in  the  muscular 
coats.  If  the  degeneration  of  the  latter  is  rapidly  effected, 
the  wall  of  the  vessel  is  likely  to  give  way.  In  this  case 
aneurysmal  dilatation  will  take  place.  More  frequently  the 
process  is  slower,  and  a  compensatory  thickening  of  the  intima 
is  brought  about  by  hyperplasia  of  the  connective-tissue 
elements  of  that  coat.  The  endarteritis  so  occasioned  leads  to 
encroachment  on  the  lumen  of  the  vessel,  and  in  some  instances 
to  such  a  degree  that  complete  obliteration  or  thrombosis 
follows. 

The  pathological  process  just  described  is  by  no  means 
uncommon  in  relation  to  the  middle  cerebral  artery  and  its 


GUMMATOUS  ARTERITIS 


139 


j^^^w^w-'^:ww' 


Fig.  39. 

a,  Gummatous  arteritis  of  the  right  middle  cerebral  artery  with  organisation  of 
the  central  clot,  b,  The  area  of  softening  in  the  right  hemisphere  resulting  from 
the  arterial  thrombosis. 


i4o^         SYPHILIS  OF  THE  NERVOUS  SYSTEM 


(, 


\ 


.-.J 


I 


b 
Fig,  40. 

a,  Gummatous  arteritis  of  the  anterior  spinal  artery  in  a  case  of  syphilitic 
meningo-myelitis.     b,  Section  of  cord  from  the  same  case. 


SYPHILITIC  MYELITIS  141 

branches,  and  herein  lies  the  explanation  of  many  cases  of 
hemiplegia  due  to  syphilitic  arteritis  and  thrombosis  which 
occur  in  young  adults  before  the  age  of  ordinary  arterio- 
sclerosis. It  is  a  disputed  point  whether  syphilitic  arteritis 
produces  calcareous  changes  such  as  are  frequent  in  arterio- 
sclerosis, but  it  is  generally  agreed  that  the  syphilitic  diathesis 
predisposes  towards  early  arterial  degeneration.  This  is 
exemplified  by  many  victims  of  congenital  syphilis,  whose 
arteries  in  early  life  resemble  those  commonly  met  with  in 
people  over  fifty  years  of  age. 

In  describing  the  morbid  anatomy  of  syphilis  of  the  nervous 
system  we  have  purposely  avoided  any  attempt  to  distinguish 
between  cerebral  and  spinal  lesions.  The  processes  in  both 
regions  are  identical,  and  it  is  common  to  find  them  coexistent 
or  developing  first  in  one  and  then  in  the  other.  From  the 
clinical  standpoint,  it  is  well  known  that  the  subject  of  cerebral 
syphilis  may  at  any  time  develop  spinal  symptoms  and  vice  versa 
unless  thorough  treatment  has  been  enforced.  Similarly,  the 
post-mortem  examination  of  a  fatal  case  of  nervous  syphilis 
nearly  always  reveals  morbid  changes  in  parts  of  the  brain  and 
spinal  cord,  other  than  that  to  which  attention  has  been 
directed  by  the  clinical  symptoms.  Further,  the  mixture 
of  coarse  syphilitic  processes,  such  as  gummatous  arteritis  and 
gummatous  meningitis,  with  the  characteristic  degenerative 
changes  of  tabes,  is  by  no  means  rare. 

4.  Syphilitic  myelitis. — This  is  by  far  the  most  common  form 
of  myelitis,  and  appears  to  affect  males  much  more  frequently 
than  females.  It  may  occur  at  almost  any  age,  but  is  more 
frequent  between  twenty  and  forty.  It  has  been  known  to 
be  the  result  of  congenital  syphilis.  The  interval  between  the 
primary  infection  and  the  spinal  disease  varies  from  a  few 
months  to  a  great  many  years,  but  the  majority  of  cases  develop 
before  five  years  have  elapsed. 

Pathogenesis. — The  term  syphilitic  myelitis  usefully  describes 
a  process  which  is  not  altogether  a  simple  one,  because  the 
influence  of  the  syphilitic  virus  upon  the  spinal  disease  is 
exerted  in  a  number  of  different  ways.  The  resulting  process 
consists  partly  of  changes  produced  by  interference  with  the 
local  circulation,  partly  of  changes  due  to .  the  diffusion  of 
toxic   substances,    and   partly   of   an   inflammatory   process 


142  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

leading  to   the  formation  of  granulomatous  or  gummatous 
material. 

Any  or  all  of  these  results  may  be  concerned  in  any  particular 
case,  but  as  a  rule  one  or  other  preponderates.  It  is  the  rule 
to  find  evidence  of  syphilitic  changes  in  the  blood  vessels 
and  meninges  over  a  much  wider  area  of  the  cord  than  the 
clinical  symptoms  have  suggested,  and  it  is  probably  often 
the  case  that  the  latter  have  been  determined  by  an  acute  or 
subacute  interference  with  the  circulation  brought  about  by 
vascular  thrombosis  of  one  or  more  important  vessels.  The 
incidence  of  syphilitic  myelitis  is  much  more  frequent  in  the 
thoracic  region  than  elsewhere,  probably  owing  to  the  fact  that 
this  part  of  the  cord  is  not  so  well  supplied  with  blood  as 
the  cervical  and  lumbo-sacral  enlargements. 

Morbid  anatomy. — The  lesion  in  syphilitic  myelitis  is  usually 
single  and  generally  limited  to  a  few  segments,  so  that  it  may 
be  generally  described  as  a  transverse  myelitis.  The  diseased 
area  is  readily  recognised  by  its  soft  consistence  and  often  by 
its  creamy  colour.  The  overlying  membranes  may  be  some 
what  opaque  and  sometimes  firmly  adherent  to  the  dura  mater. 
Difficulty  may  be  experienced  in  separating  the  latter  from 
the  leptomeninges  and  cord  itself. 

Having  regard  to  the  variety  of  the  processes  involved,  the 
changes  in  each  kind  of  tissue  are  best  considered  separately. 

(a)  The  blood  vessels. — The  vascular  changes  are  of  three 
chief  types. 

(i)  Moderate  cellular  infiltration  of  the  adventitial  sheaths 
with  thickening  of  the  intima  sufficient  to  produce  diminution 
or  complete  occlusion  of  the  lumen. 

(2)  Excessive  perivascular  cellular  infiltration  with  little 
or  no  endarteritis.  In  such  cases  there  may  be  no  evidence  of 
actual  obstructive  thrombosis,  although  slowing  of  the  circula- 
tion and  blood  stasis  is  suggested  by  the  excess  of  white 
corpuscles.  Around  such  vessels  there  may  be  evidence  of 
considerable  toxic  degeneration,  or  an  extension  of  the  cellular 
proliferation  into  the  neighbouring  tissues. 

(3)  Paralytic  vaso-dilatation  with  very  moderate  peri- 
vascular infiltration  and  with  no  obvious  thickening  of  the 
vessel  walls.  This  is  associated  with  capillary  thrombosis  and 
profound  alterations  in  the  nervous  elements.     The  appearance 


SYPHILITIC  MYELITIS  143 

produced  is  one  of  general  hyperaemia  involving  the  white  and 
grey  matter,  and  accompanied  by  degenerative  changes  in  the 
myelin  sheaths  and  the  ganglion  cells. 

(b)  The  neuroglia  offers  much  more  resistance  than  do  the 
nervous  elements  to  disturbances  in  the  circulation.  In  areas 
of  complete  necrosis  it  may  succumb  with  everything  else, 
the  neuroglial  cells  rapidly  losing  their  staining  reaction  and 
with  the  fibres  taking  part  in  the  general  liquefaction.  In  other 
regions  where  the  vascular  changes  have  not  been  so  profound 
the  neuroglial  cells  survive  when  more  specialised  structures 
are  destroyed.  Under  these  circumstances  they  tend  to 
increase  in  size  and  to  become  multinuclear.  Later  on  they 
proliferate  and  take  a  leading  part  in  the  process  of  repair, 
sending  out  long  interlacing  fibres  in  all  directions.  They 
probably  give  origin  to  some,  at  any  rate,  of  the  large  granular 
cells  which  act  as  scavengers,  and  which,  at  first  distributed 
in  the  tissues,  are  later  collected  in  the  perivascular  lymph 
channels. 

With  the  neuroglial  changes  must  also  be  mentioned  the 
gummatous  infiltration  which  occasionally  goes  hand  in  hand 
with  the  circulatory  disturbances.  Sometimes  it  is  a  pre- 
dominant feature  of  the  process,  and  a  true  gumma,  with 
the  characteristic  central  degeneration  and  caseation,  may 
occupy  a  considerable  part  of  the  transverse  area  of  the  cord. 
On  the  other  hand,  there  may  be  a  more  diffuse  condition 
starting  near  the  surface  and  spreading  in  from  the  vessels 
and  meninges,  to  which  the  term  gummatous  meningo-myelitis 
is  quite  appropriate. 

(c)  The  nervous  elements. — Degeneration  of  the  myelin  sheaths 
and  retrograde  changes  in  the  ganglion  cells  result  either  from 
the  circulatory  disturbances  or  from  the  diffusion  of  toxic 
substances.  The  myelin  sheaths  swell,  disintegrate  and 
disappear,  leaving  axis  cylinders  which  may  subsequently 
undergo  degeneration  or  destruction.  The  ganglion  cells  in 
the  affected  areas  display  the  usual  chromatolytic  changes  and 
are  not  infrequently  completely  destroyed.  Secondary  de- 
generations both  in  the  ventral  roots  and  in  the  long  tracts  of 
the  cord  are  common  enough. 

(d)  The  leptomeninges. — Infiltration  of  the  pia- arachnoid 
with  cells  chiefly  of  the  mononuclear  type  is  almost  of  universal 


144  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

occurrence  in  this  disease,  and  is  usually  followed  in  later  stages 
by  well-marked  thickening  and  adhesions  of  the  membrane. 
Hypertrophy  of  the  arterial  muscular  coats  is  frequently  seen, 
and  even  the  veins  may  display  an  obliterative  phlebitis.  Some- 
times the  latter  present  a  laminated  appearance,  layers  of 
round  cells  being  separated  from  each  other  by  strands  of 
connective  tissue,  with  the  result  that  their  bulk  is  often 
as  great  as  that  of  the  arteries. 

Processes  of  repair  are  essentially  the  same  as  those  described 
in  other  forms  of  myelitis,  and  the  examination  of  a  focal 
lesion  a  year  or  more  after  the  acute  stage  may  reveal  nothing 
characteristic  of  its  original  nature. 

It  is  worth  while  remembering  that  more  than  one  syphilitic 
lesion  maybe  found  in  the  central  nervous  system,  and,  further, 
that  a  cord  may  at  the  same  time  be  the  seat  of  a  localised 
syphilitic  lesion  and  of  a  parasyphilitic  process,  such  as  tabes 
dorsalis.  We  have  even  met  with  a  cerebral  syphilitic  throm- 
bosis, a  syphilitic  myelitis,  and  the  appearances  produced  by 
tabes  in  the  same  subject. 

The  relationship  of  the  anatomical  to  the  clinical  phenomena. — 
The  clinical  phenomena  may  be  divided  into  those  which  are 
local  and  those  which  are  remote.  The  local  phenomena 
include  atrophic  palsy  of  the  muscles  innervated  by  the  segments 
which  are  the  seat  of  the  disease,  and  also  sensory  and  reflex 
changes  corresponding  to  them.  The  remote  phenomena 
depend  upon  the  loss  of  conduction  of  impulses  through  the 
diseased  areas,  and  are  illustrated  by  the  spastic  forms  of 
paraplegia  and  loss  of  sensation  in  those  parts  of  the  body 
innervated  from  the  cord  below  the  level  of  the  lesion.  In 
the  infective  form  of  myelitis  it  is  quite  common  for  one  of 
the  spinal  enlargements  to  be  the  seat  of  the  disease,  and  an 
atrophic  palsy  of  the  arms  with  a  spastic  paralysis  affecting  the 
trunk  and  limbs  is  by  no  means  rare.  Owing  to  the  special 
incidence  of  the  syphilitic  process  on  the  thoracic  region  of  the 
cord,  a  spastic  paraplegia  is  the  most  prominent  clinical  feature, 
evidences  of  atrophic  palsy  in  the  trunk  muscles  being  less 
easily  detected  than  they  are  in  the  limbs.  When  a  transverse 
lesion  is  very  complete  in  the  early  stages  of  myelitis, 
whether  it  be  of  the  infective  or  syphilitic  type,  the  resulting 
paraplegia  may  at  any  rate  for  a  time  be  flaccid  in  character. 


TABES  DORSALIS  145 

spasticity  supervening  as  time  goes  on.  Both  forms  are 
associated  with  disturbances  of  the  sphincters,  either  because 
of  the  incidence  of  the  disease  on  the  lumbo-sacral  centres  or 
because  of  the  interference  in  the  conducting  paths  when  the 
lesion  lies  above  those  centres.  A  syphilitic  lesion  limited 
to  one-half  of  the  spinal  cord  may  produce  the  clinical  pheno- 
mena known  as  Brown-Sequard's  paralysis. 

The  condition  usually  described  as  Erh's  syphilitic  paraplegia 
may  be  briefly  referred  to  here.  Little  is  known  about  the 
morbid  anatomy  of  these  cases  because  many  of  them  which 
have  corresponded  to  the  clinical  diagnosis  have  been  shown 
post  mortem  to  be  really  the  subjects  of  a  transverse  syphilitic 
myelitis  in  the  dorsal  region  of  the  cord  with  the  usual  ascending 
and  descending  tract  degenerations.  On  the  other  hand, 
there  is  some  evidence  to  show  that  syphilitic  toxins  may 
produce  a  degeneration  of  the  long  tracts  in  the  posterior 
and  lateral  columns  without  the  intervention  of  any  specific 
changes  in  the  blood  vessels  or  meninges  of  the  spinal  cord. 

5 .  Tahes  dorsalis. — So  far  as  is  known,  the  only  essential  factor 
in  the  aetiology  of  tabes  is  syphilitic  infection,  either  congenital 
or  acquired.  Probably  the  majority  of  physicians  would 
agree  that  tabes  does  not  occur  without  syphilis,  although 
evidence  sufficient  for  proof  of  such  a  view  is  not,  and  of  course 
never  can  be,  forthcoming.  Originally,  the  connection  between 
tabes  and  syphilis  was  inferred  merely  from  clinical  observations ; 
recently  laboratory  methods  have  shown  that  a  positive  Wasser- 
mann  reaction  can  be  obtained  in  a  large  majority  of  tabetic 
patients  in  both  the  blood  and  cerebro-spinal  fluid. 

Tabes  is  far  more  common  in  the  male  than  in  the  female 
sex,  an  indication  perhaps  that  other  factors,  such  as  prolonged 
and  severe  physical  exertion,  may  play  an  important  additional 
part  in  producing  tabes  in  syphilised  individuals.  The  in- 
fluence of  age  is  not  important  in  itself,  although  there  appears 
to  be  a  definite  relationship  between  the  age  at  which  syphilis 
is  contracted  and  that  at  which  tabetic  symptoms  commence. 
Speaking  roughly,  there  is  an  interval  averaging  from  eight 
to  twelve  years  between  these  two  dates.  On  the  other  hand, 
there  are  exceptional  cases  in  which  tabes  follows  syphilis  after 
the  lapse  of  only  two  or  three  years.  Syphilitic  infection  is  most 
common  between  twenty  and  twenty-five  years  of  age,  and  it 


146         SYPHILIS  OF  THE  NERVOUS  SYSTEM 

is  not  surprising,  therefore,  to  find  that  the  earUest  signs  of 
tabes  are  most  frequently  noticed  in  the  fourth  decade  of  Hfe. 
Cases  resembUng  tabes  among  children  are  very  uncommon,  but 
there  are  a  few  tabetic  patients  whose  symptoms  can  be  traced 
back  to  early  childhood,  and  who  may  have  been  the  victims 
of  congenital  syphilis  or  of  an  infection  acquired  in  infancy. 

So  small  a  proportion  of  individuals  who  acquire  syphilis 
become  tabetic  that  it  is  natural  to  look  for  other  factors  in- 
fluencing the  incidence  of  the  disease.  Prolonged  over-exertion 
has  already  been  mentioned  as  a  possible  explanation  of  the 
peculiar  susceptibility  of  the  male  sex,  and  many  observations 
are  on  record  showing  that  constant  exercise  of  particular  parts 
of  the  body  has  appeared  to  determine  the  first  symptoms 
of  the  malady.  An  artist  may  begin  with  optic  atrophy,  a 
postman  with  ataxic  gait,  or  a  wood-turner  with  tabetic 
symptoms  limited  to  the  upper  extremities,  the  so-called 
cervical  form  of  tabes.  This  line  of  argument,  however, 
cannot  be  pushed  too  far  as  many  cases  present  contradictory 
features. 

We  are  so  accustomed  to  hear  that  exposure  to  cold,  various 
excesses  and  abuses,  and  especially  injuries,  are  determining 
causes  of  disease  that  a  feeling  of  disappointment  might  be 
engendered  if  they  were  not  mentioned  in  this  connection. 
From  a  pathological  point  of  view,  it  is  impossible  or  very 
difficult  to  believe  that  trauma  can  materially  help  in  the  pro- 
duction of  such  a  disease  as  tabes,  although  it  cannot  be  denied 
that  a  shock  may  reveal  or  bring  into  prominence  certain 
symptoms  which  the  patient  might  otherwise  have  continued 
to  ignore — at  any  rate,  for  a  time.  The  mere  fact  that  it  is 
within  our  experience  that  one  or  two  cases  of  tabes  have 
realised  their  first  symptoms  in  the  sequel  of  an  accident  is  no 
proof  whatever  that  trauma  can  take  any  part  in  the  production 
of  this  disease. 

It  is  sometimes  taught  that  although  a  patient  may  become 
ataxic  after  an  injury,  it  must  not  be  assumed  that  his  disease 
originated  in  this  way  until  it  is  ascertained  that  there  is  no 
previous  history  of  lightning  pains,  squint,  etc.  Even  then 
such  an  assumption  is  not  justified,  as  we  have  had  personal 
experience  of  detecting  undoubted  signs  of  tabes  in  several 
persons  who  have  not  sought  medical  advice,  and  who,  in  answer 


TABES  DORSALIS  147 

to  questions,  have  assured  us  that  they  have  nothing  whatever 
to  complain  of.  It  is  inaccurate  to  say  that  a  person  has  not 
been  ataxic  because  neither  he  nor  his  friends  have  noticed 
any  abnormahty  of  gait.  Many  tabetics  can  walk  naturally 
and  easily,  but  come  to  hopeless  grief  when  asked  to  toe  and 
heel  a  line.  They,  too,  suffer  from  ataxy,  although  they  may 
not  know  it. 

Alcoholism  does  not  appear  to  be  closely  related  to  tabes, 
although  of  course  it  would  be  easy  to  cite  numerous  cases 
in  which  alcoholic  excess  was  admitted. 

We  are  unlikely  to  be  far  wrong  if  we  conclude  that  uncured 
syphilis  (and  our  older  views  on  the  curability  of  syphilis  have 
received  rude  shocks  in  recent  years)  is  the  one  essential 
aetiological  factor  in  the  production  of  locomotor  ataxy. 

Pathogenesis. — From  a  clinical  standpoint,  tabes  is  a  disease 
characterised  by  a  more  or  less  symmetrical  affection  of  the 
lower  afferent  neurons  with  the  occasional  addition  of  motor 
palsies.  The  affection  of  the  afferent  neurons  is  peculiar  in 
that  some  afferent  impulses  are  destroyed  while  others  remain 
intact.  Those  impulses  connected  with  sense  of  position,  and 
those  associated  with  deep  and  superficial  pain,  are  apt  ta 
succumb  before  those  which  are  of  tactile  origin.  When  we 
consider  that  all  the  various  forms  of  afferent  impulses  must 
reach  the  central  nervous  system  through  the  posterior  roots 
or  analogous  cranial  nerves,  it  is  difficult  to  believe  that  any 
gross  lesion,  such  as  is  produced  by  meningeal  inflammation, 
can  so  affect  the  posterior  roots  that  only  fibres  of  particular 
function  are  picked  out  for  destruction.  For  this  reason  the 
view  that  the  essential  lesion  in  tabes  is  a  syphilitic  meningitis 
involving  the  posterior  roots,  either  on  the  surface  of  the  cord 
or  at  the  point  where  they  pass  through  the  dura  mater,  is  one 
which  is  difficult  to  support.  Moreover,  it  has  not  been  con- 
clusively demonstrated  that  meningeal  changes  are  constant 
and  early  phenomena  in  the  pathology  of  the  disease.  The 
French  school  which  favours  the  view  that  there  exists  a 
radiculitis  at  the  point  where  the  roots  pierce  the  dural  sheath 
has  not  explained  satisfactorily  the  escape  of  the  anterior  root 
fibres. 

The  older  conception  of  the  disease,  which  assumed  a  primary 
sclerosis  of  the  posterior  columns,  failed  to  hold  its  place  when  it 


148  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

was  shown  that  the  distribution  of  degeneration  within  the  cord 
corresponded  closely  to  the  distribution  of  exogenous  fibres. 
No  primary  sclerotic  process  of  the  cord  itself  could  be  credited 
with  the  power  of  discrimination  between  fibres  of  intra-  and 
extra-medullary  origin.  Modern  pathologists  have  tended  to 
look  upon  neuroglial  proliferation  and  meningeal  inflammations 
as  secondary  or  accidental  phenomena,  and  to  regard  the  pro- 
gressive degeneration  of  the  lower  afferent  neurons  as  the 
primary  and  fundamental  morbid  process. 

It  is  reasonable  to  regard  this  destruction  of  afferent  neurons 
as  thejresult  of  a  degeneration  brought  about  by  syphilitic 
toxins  and  to  put  tabes  in  the  same  class  as  other  toxic 
conditions  of  the  nervous  system,  from  which  it  differs  chiefly 
in  the  choice  of  the  neurons  affected.  We  are  familiar  with  the 
effects  of  alcohol,  diphtheria,  etc.,  on  peripheral  neurons,  and 
we  see  exceptional  cases  in  which  those  poisons  produce 
clinical  phenomena  closely  resembling  those  of  tabes.  The 
chief  difference  between  a  diphtheritic  infection  and  a  syphilitic 
infection  lies  in  the  difliculty  in  eradicating  the  latter  and, 
consequently,  in  its  profound  and  enduring  effects  on  those 
neurons  which  are  specifically  susceptible  to  its  influence. 

It  has  been  argued  that  the  long  interval  between  syphilitic 
infection  and  the  onset  of  tabes  makes  the  analogy  between 
the  latter  and  such  a  toxic  process  as  post-diphtheritic  palsy 
untenable.  On  the  other  hand,  we  do  not  expect  alcoholic 
neuritis  to  follow  the  first  indulgence  in  alcohol,  but  regard  it 
as  the  result  of  the  long-continued  exposure  of  the  peripheral 
neurons  to  the  influence  of  that  poison.  Many  cases  of  alcoholic 
neuritis  recover  if  the  patient  is  prevented  from  drinking, 
but  others  die  or  remain  permanently  paralysed  even  after 
indulgence  in  the  drug  has  ceased. 

It  must  be  remembered  that  although  the  lower  afferent 
neurons  are  the  site  of  most  changes  in  tabes,  other  neurons, 
afferent  and  efferent,  may  also  be  affected.  Optic  atrophy  and 
oculo-motor  palsies  are  common  examples  of  this  observation. 

The  frequent  presence  of  a  positive  Wassermann  reaction  in 
cases  of  tabes  has  already  been  noted,  and,  as  this  reaction  is  an 
indication  of  the  presence  of  an  active  virus  rather  than  a  clue 
to  past  syphilis,  there  is  strong  reason  for  regarding  tabes  as  a 
definitely  syphilitic  process. 


TABES  DORSALIS  149 

Morbid  anatomy. — We  are  no  longer  satisfied  with  sclerosis 
of  the  posterior  spinal  columns  as  a.  description  of  the  morbid 
anatomy  of  tabes,  and  we  owe  our  more  exact  knowledge  of 
the  process  to  observation  on  the  development  and  on  the 
minute  composition  of  the  posterior  columns.  A  true  apprecia- 
tion of  the  pathological  changes  in  tabes  has  been  derived  from 
the  study  of  many  cases,  especially  of  early  cases,  and  the 
examination  of  one  long-standing  example  of  the  disease  may 
easily  give  rise  to  erroneous  conclusions.  The  essential 
lesion  is  a  slow,  progressive  degeneration  of  the  lower 
afferent  neurons  of  the  spinal  cord  and  brain-stem,  and  to 
this  must  be  added  the  results  of  accidental  and  secondary 
processes. 

In  order  to  appreciate  the  essential  lesion  of  tabes  it  is 
desirable  to  recall  certain  anatomical  facts  about  the  com- 
position of  the  posterior  columns  of  the  cord.  The  dorsal 
columns  are  composed  of  medullated  nerve  fibres,  some  of  which 
are  derived  from  spinal  cells  (endogenous),  and  the  remainder 
of  which  are  the  central  prolongations  of  the  dorsal  root 
ganglion  cells  (exogenous).  The  endogenous  fibres  probably 
serve  to  connect  the  cells  of  one  spinal  segment  with  those  of 
other  spinal  segments  above  or  below.  They  occupy  chiefly 
the  ventro-lateral  margin  of  the  columns,  and  form  a  band 
known  as  the  cornu-commissural  zone.  Degeneration  of 
this  zone  is  not  an  essential  part  of  the  morbid  anatomy  of 
tabes,  but  it  occurs  in  long-standing  cases — in  some  parts  of  the 
cord  at  least — owing  to  the  large  amount  of  neuroglial  over- 
growth which  is  a  direct  result  of  the  destruction  of  neigh- 
bouring nerve  fibres.  It  may  be  assumed  that  this  loss  of 
endogenous  fibres  is  brought  about  by  their  strangulation  in 
the  contracting  glial  tissue  and  perhaps  by  reason  of  inter- 
ference with  their  vascular  and  lymphatic  supply.  There  is  a 
system  of  descending  fibres  in  the  posterior  columns  which 
may  be  endogenous  in  origin,  but  which  more  probably  re- 
presents the  descending  branches  of  exogenous  root  fibres.  It 
goes  by  the  name  of  the  "  comma  tract  "  in  the  cervical  and 
upper  thoracic  region,  the  "  septo-marginal  tract  "  in  the  lower 
thoracic  region,  the  "  oval  field  of  Flechsig  "  in  the  lumbar  region, 
and  the  "  median  triangle  "  in  the  sacral  region.  Surviving 
fibres  of  this  system  are  to  be  found  in  the  lower  segments  of 


150  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

the  cord  in  cases  of  lumbo-sacral  tabes  even  when  the  greater 
part  of  the  posterior  columns  are  sclerosed. 

The  exogenous  fibres  are  those  which  enter  by  the  dorsal 
roots  at  different  levels.  These  may  be  divided  into  short, 
medium,  and  long  fibres.  The  short  fibres  pass  straight  into 
the  grey  matter  of  the  corresponding  segment,  and  are  dis- 
tributed to  form  connections  of  some  kind  with  the  ventral 
and  dorsal  cornual  cells.  The  medium  fibres  pass  upwards 
to  other  levels,  but  eventually  turn  inwards  to  arborise  around 
the  cells  of  Clarke's  column.  In  their  passage  upwards  they 
become  displaced  from  their  position  on  the  edge  of  the  dorsal 
horn  to  form  a  band  of  fibres  called  the  middle  root  zone  or 
"  bandelet te  "  of  Pierret.  This  displacement  is  brought  about 
by  the  successive  entry  of  higher  dorsal  roots,  and  if  the 
latter  chance  to  be  healthy,  while  the  lower  fibres  are  atrophied, 
the  bandelette  becomes  a  conspicuous  object  between  two 
masses  of  healthy  tissue.  The  long  fibres  are  those  which  are 
destined  for  the  nuclei  gracilis  and  cuneatus  at  the  upper 
extremity  of  the  cord.  These,  too,  are  gradually  displaced 
backwards  and  towards  the  dorsal  median  septum,  those 
belonging  to  the  lowest  roots  eventually  occupying  the  column 
of  Goll,  which  becomes  present  as  a  distinct  band  of  fibres  about 
the  mid- thoracic  region. 

The  essential  lesion  of  tabes  is  the  degeneration  of  these  central 
prolongations  of  the  dorsal  root  ganglion  cells,  and  it  is 
important  to  note  that  the  process  begins  earlier  in  that 
portion  of  the  fibres  which  lies  within  the  cord  than  in  the 
dorsal  roots  themselves.  It  is  probable,  although  difficult  of 
demonstration,  that  the  descending  branches  of  the  exogenous 
fibres  also  undergo  degenerative  changes.  What  has  been 
described  in  regard  to  the  afferent  root  fibres  applies,  in 
some  cases  at  least,  to  the  analogous  fibres  of  certain  cranial 
nerves  such  as  the  glosso-pharyngeal,  the  auditory,  and  the 
trigeminal. 

In  addition  to  the  destruction  of  fibres  in  the  dorsal 
columns,  there  are  other  demonstrable  changes  probably  of 
secondary  origin.  The  neuroglial  tissue  proliferates,  the  vessel 
walls  become  thickened  and  hyaline,  and  the  pial  trabeculae 
are  distinctly  more  substantial  and  prominent.  Thickening 
of  the  pia-arachnoid  membrane  on  the  dorsal  surface  of  the 


TABES  DORSALIS 


151 


Fig.  41. 

Two  sections  illustrating  the  degeneration  in  the  dorsal  columns  in  tabes 
dorsalis  (Weigert-Pal). 


15^  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

cord  is  also  a  conspicuous  feature  of  cases  of  any  standing. 
The  dorsal  root  ganglion  cells  are  usually  intact.  In  rare 
cases  they  may  present  atrophic  changes,  and  not  uncommonly 
the  connective-tissue  elements  by  which  they  are  surrounded 
show  signs  of  proliferation.  The  peripheral  prolongations  of 
the  root  ganglion  cells  are  occasionally  observed  to  be  atrophied, 
especially  towards  their  extremities. 

Rarely  there  is  found  a  localised  or  widespread  degeneration 
of  the  lower  motor  neurons  of  cranial  or  spinal  origin.  In  such 
instances  the  central  cells  may  be  seen  to  be  decreased  in  number, 
while  those  which  survive  display  simple  atrophic  or  chromo- 
lytic  changes.  The  corresponding  efferent  roots,  peripheral 
nerves,  and  muscle  fibres  present  evidence  of  the  secondary 
atrophy  which  one  would  naturally  expect. 

Recent  investigation  has  confirmed  the  older  theory  that  the 
sympathetic  system  is  involved,  and  Roux  has  found  definite 
degeneration  of  the  afferent  myelinated  fibres,  to  which  he 
attributes  many  of  the  visceral  symptoms  characteristic  of 
the  disease. 

Many  attempts  have  been  made  to  discover  the  anatomical 
basis  of  the  Argyll-Robertson  pupil,  but  the  problem  has  not 
yet  been  solved  in  such  a  way  as  to  satisfy  all  critics.  De- 
generation of  the  optic  nerve  begins  near  the  disc  and  spreads 
towards  the  chiasma.  Some  doubt  has  been  expressed  as 
to  whether  this  process  is  a  primary  one  or  an  atrophy  secondary 
to  a  chronic  interstitial  change  in  the  nerve.  The  ganglion 
cells  of  the  retina  are  not  usually  affected. 

The  gross  abnormalities  of  the  central  nervous  system  in  cases 
of  tabes  are  generally  striking  and  characteristic.  The  dorsal 
roots,  most  frequently  those  of  the  lower  thoracic  and  lumbo- 
sacral regions,  are  reduced  in  calibre,  and,  compared  with  the 
opaque  white  ventral  roots,  present  a  greyish  semi-translucent 
appearance.  The  surface  of  the  dorsal  columns,  instead  of 
being  convex,  is  often  flattened  and  sometimes  even  concave, 
owing  to  the  contraction  of  the  glial  tissue  and  the  destruction 
of  nerve  fibres.  On  section  they  present  the  same  contrast 
to  the  ventro-lateral  columns  as  do  the  dorsal  to  the  ventral 
roots.  In  the  brain,  atrophy  of  the  optic  and  perhaps  of  other 
afferent  cranial  nerves  may  be  detected  by  the  naked  eye, 
while  there  is  frequently  some   shrinking  of  the  precentral 


TABES  DORSALIS  153 

convolutions,  especially  in  cases  complicated  by  paralytic 
dementia.  Some  thickening  of  the  meninges,  particularly  the 
pia-arachnoid  on  the  dorsal  surface  of  the  cord,  is  usually  to 
be  noticed. 

In  addition  to  what  we  have  termed  the  essential  lesions  of 
tabes,  evidence  of  tertiary  syphilitic  processes  in  the  central 
nervous  system  is  not  so  very  uncommon.  In  one  case  there 
was  a  patch  of  softening  in  the  pons  due  to  syphilitic  arteritis 
of  the  basilar  artery;  in  another  the  tabetic  changes  in  the 
spinal  cord  were  complicated  by  an  extensive  gummatous 
pachymeningitis.  Syphilitic  aortitis,  with  or  without  aneu- 
rysm, is  another  complication  of  tabes  which  is  sufficiently 
frequent  to  deserve  notice. 

The  osseous  and  arthritic  changes,  so  well  described  by 
Charcot,  are  interesting.  The  bones  tend  to  become  brittle 
owing  to  the  dilatation  of  the  Haversian  canals  and  the 
absorption  of  phosphates.  Spontaneous  fractures  which  fail 
to  unite  properly  are  by  no  means  uncommon  in  the  long  bones. 
The  capsules  and  synovial  membranes  of  the  Charcot  joints  are 
thickened.  The  cavities  contain  an  excess  of  fluid,  and  the 
cartilages  are  ulcerated  or  entirely  destroyed.  Erosion  of  the 
epiphysial  end  of  the  bone  may  take  place  in  advanced 
cases,  and  along  with  the  destructive  process  there  is  often 
a  crop  of  bony  growths  in  connection  with  the  synovial 
membranes.  The  knee,  hip  and  tarsal  joints  are  favourite  sites 
for  this  change,  and  the  deformity  is  often  increased  by 
the  strain  on  the  ligaments  and  tendons  being  more  than 
they  can  bear. 

The  relation  of  the  anatomical  to  the  clinical  phenomena. — 
The  fundamental  symptoms  of  tabes  are  due  to  disturbance 
of  afferent  impulses,  and  how  the  latter  come  to  be  disturbed 
has  been  already  demonstrated.  We  have  to  remember, 
however,  that  the  process  is  a  gradual  one,  and  that  before 
impulses  are  cut  off  entirely  there  are  stages  in  which  they  are 
modified,  impaired  or  delayed  in  transmission.  In  this  way 
we  may  understand  the  various  forms  of  paraesthesiae,  of  hyper- 
aesthesia,  and  of  delayed  sensation  so  common  in  the  history 
of  the  disease.  Similarly,  we  may  correlate  the  disturbance 
of  non-sensory  afferent  impulses  with  our  anatomical  data. 
The  paths  conveying  impulses  necessary  for  co-ordinate  move- 


154  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

ment  from  the  structures  of  the  periphery,  especially  from  the 
feet  and  legs,  are  involved  in  the  decay  of  afferent  neurons, 
with  the  result  that  there  is  an  imperfect  transport  service  both 
to  the  cerebrum  via  the  dorsal  columns  and  dorsal  column 
nuclei,  as  well  as  to  the  cerebellum  via  the  medium  fibres, 
Clarke's  column,  and  the  direct  cerebellar  tract.  In  either  case 
disturbance  of  equilibrium  must  result,  which  may  or  may  not 
be  compensated  for  by  visual  and  vestibular  impulses  when  the 
paths  of  the  latter  remain  intact. 

The  explanation  of  the  severe  lightning  pains  in  cases  in 
which  pain  sensibility  is  profoundly  impaired  is  a  difficult  one, 
especially  if  we  regard  these  active  phenomena  as  the  result 
of  a  slow  katabolic  process  of  degeneration,  rather  than  as  the 
result  of  an  irritating  toxic  influence.  The  diminution  of 
tendon  jerks  is  only  to  be  expected  in  view  of  the  involvement 
of  the  afferent  part  of  the  reflex  arc  represented  by  the  short 
fibres  entering  with  the  dorsal  roots  and  proceeding  direct 
to  the  ventral  cornual  cells.  The  problem  of  the  Argyll- 
Robertson  pupil  still  awaits  solution. 

6.  General  paralysis  of  the  insane — Aetiology. — A  history  of 
syphilis  is  obtained  in  from  75  to  85  per  cent,  of  cases  of  this 
disease,  and  this  percentage  may  be  regarded  as  sufficient  to 
prove  the  dependence  of  general  paralysis  upon  luetic  infec- 
tion :  certainly  no  higher  percentage  can  be  obtained  in  cases  of 
gumma  in  various  parts  of  the  body.  Juvenile  general 
paralysis  occurs  in  the  victims  of  congenital  syphilis.  A 
positive  Wassermann  reaction  is  obtained  from  the  blood 
serum  and  cerebro-spinal  fluid  in  at  least  90  per  cent,  of  cases. 
An  attempt  to  infect  general  paralytics  with  syphilis  has 
proved  a  failure.  Tabes  and  general  paralysis  are  not  in- 
frequently associated  in  the  same  patient,  and  there  are  many 
instances  on  record  in  which  a  husband  and  wife  have  both 
suffered  from  one  or  other  of  these  so-called  parasyphilitic 
diseases. 

Recently  conclusive  proof  of  the  aetiology  of  the  disease 
has  been  afforded  by  the  discovery  of  the  Spirochaeta  pallida 
in  the  cortex  of  general  paralytics  in  a  very  large  proportion 
of  cases,  and  the  occasional  discovery  of  this  organism  in  the 
cerebro-spinal  fluid. 

Although  syphilis  must  be  the  essential  cause  of  the  malady 


GENERAL  PARALYSIS  155 

under  consideration,  it  is  open  to  discussion  whether  other 
factors  may  play  less  important  parts  in  determining  the  onset 
of  symptoms.  It  is  usual  and  perhaps  justifiable  to  refer  to 
excessive  mental  activity  and  prolonged  anxiety  and  strain 
in  this  connection,  but  the  exact  value  of  such  influences  is 
largely  a  matter  of  guesswork.  Alcoholic  and  venereal  ex- 
cesses are  as  commonly  early  symptoms  of  the  disease  as 
predisposing  causes.  There  is  no  satisfactory  evidence  that 
injuries  can  initiate  the  morbid  process. 

The  onset  of  general  paralysis  is  commonly  during  the 
fourth  and  fifth  decades  of  life,  and  this  corresponds  closely 
to  the  age  incidence  of  tabes.  Juvenile  general  paralysis 
generally  displays  itself  between  the  ages  of  eight  and  eighteen. 
As  in  tabes,  so  in  general  paralysis,  the  male  sex  is  more  often 
attacked  than  the  female. 

Pathogenesis. — Although  the  histological  changes  in  the 
central  nervous  system  are  characteristic  and  well  known, 
it  is  still  a  matter  of  debate  as  to  how  far  the  process  may  be 
regarded  as  primarily  degenerative,  or  how  far  the  degeneration 
of  neurons  is  dependent  upon  toxic  and  vascular  influences. 
It  must  be  admitted,  in  any  case,  that  many  of  the  classical 
phenomena  of  the  disease  are  directly  due  to  circulatory  and 
inflammatory  disturbances.  Probably  the  neuronic  decay  is 
the  initial  lesion,  although  its  progress  may  be  accelerated  by 
venous  stasis,  changes  in  the  arterial  walls,  neuroglial  prolifera- 
tion, meningeal  thickening,  and  the  influence  of  poisons  re- 
sulting from  tissue  disintegration. 

Morbid  anatomy. — The  gross  changes  observed  on  the  post- 
mortem table  are  somewhat  various  and  dependent  upon  the 
stage  of  the  disease  at  which  death  takes  place.  In  long- 
standing cases  terminated  by  exhaustion  or  some  low  form 
of  pneumonia  or  broncho-pneumonia,  it  is  usual  to  find  con- 
siderable general  wasting  of  the  central  nervous  system.  In 
others,  which  have  ended  with  some  sudden  seizure,  the  atrophy 
may  be  less  general  and  less  remarkable. 

The  skull  bones  are  usually  denser  than  normal  and  more 
closely  adherent  to  the  subjacent  dura.  Beneath  the  latter 
there  may  be  old  or  recent  extravasations  of  blood,  giving  rise 
to  the  condition  known  as  pachymeningitis  interna  haemor- 
rhagica.     The  weight  of  the  brain  is  diminished  as  a  whole, 


156  SYPHILIS  OF  THE  NERVOUS  SYSTEM 

and  that  of  the  cerebrum  proportionately  more  so  than  that 
of  the  brain-stem  and  cerebellum.  The  pia-arachnoid  mem- 
brane is  thickened  and  often  opalescent  in  appearance,  especially 
over  the  fronto-parietal  region. .  In  the  same  area  the  convo- 
lutions are  markedly  atrophic,  and  the  intervening  sulci  are 
filled  with  slightly  turbid  fluid.  Sections  through  the  hemi- 
sphere disclose  narrowing  and  vascularity  of  the  grey  matter, 
and  obscuration  of  the  lines  of  Gennari  and  Baillarger.  The 
white  matter  is  soft  and  oedematous.     The  ventricles  may  be 


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Fig.  42. 

Section  from  pvae-Rolandic  cortex  in  a  case  of  general  paralysis  of  the  insane, 
showing  the  presence  of  large  numbers  of  small  round  cells  in  the  neighbourhood 
of  a  vessel,  not  confined  to  the  perivascular  sheath. 

dilated,  and  their  ependymal  lining  is  practically  always 
somewhat  granular :  that  of  the  fourth  ventricle  is  often  described 
as  "  frosted."  Atrophic  changes  in  the  optic  nerves  and  some- 
times in  the  long  tracts  of  the  spinal  cord  may  be  visible  to 
the  naked  eye. 

Under  the  microscope  the  most  characteristic  changes  are  to 
be  found  in  the  fronto-central  parts  of  the  cerebral  hemispheres. 
Here  the  tissue  is  seen  to  be  highly  vascular,  owing  partly 
to  the  dilatation  of  vessels,  and  partly  to  the  presence  of 
sprouting   new    capillaries.     The    vessel    walls    are    rendered 


GENERAL  PARALYSIS 


157 


Fig.  43. 

Section  of  first  lumbar  segment  in  a  case  of  general  paralysis  of  the  insane, 
showing  degeneration  in  lateral  columns. 


Fig.  44. 
Section  from  lumbar  cord  in  a  case  of  taboparesis. 


158  GENERAL  PARALYSIS 

thicker  than  normal  by  the  proUferation  of  endotheUal  cells, 
and  by  the  presence  of  numerous  lymphocytes  and  plasma 
cells  crowding  the  perivascular  spaces.  Here  and  there  may 
be  seen  isolated  elongated  cells  resembling  collapsed  capil- 
laries. The  neuroglial  cells  of  all  kinds  are  increased  in  number, 
and  many  spider  cells  may  be  detected  in  the  vicinity  of 
vessels  with  their  processes  impinging  on  the  latter.  The 
neuroglial  fibrils  beneath  the  pia  are  abundant  and  form  a  kind 
of  felt  work  in  that  situation.  The  natural  arrangement  of 
nerve  cells  is  upset,  and  difficulty  is  experienced  in  recognising 
the  different  layers.  Pyramidal  cells  are  destroyed,  altered, 
or  displaced;  their  processes  are  often  ruptured  and  their 
dendrites  decayed.  Chromatolysis,  vacuolation  and  eccentric 
position  of  nuclei  are  prominent  features  in  many  cases.  The 
higher  association  systems  of  neurons  suffer  the  most,  and  the 
supragranular  pyramidal  cells  are  especially  involved.  Sections 
stained  by  the  Weigert-Pal  method  reveal  atrophy  of  the 
tangential,  supra-  and  intra-radial  fibres.  With  the  Marchi 
stain,  scattered  degeneration  may  be  seen  in  many  systems 
throughout  the  central  nervous  system.  Degeneration  may  be 
traced  in  the  pyramidal  tracts  of  the  brain-stem  and  spinal  cord, 
and  in  some  cases  in  which  tabetic  processes  have  been  present, 
characteristic  sclerosis  may  be  found  in  the  dorsal  columns. 
Occasionally  the  cells  of  the  ventral  horns  and  of  the  dorsal 
root  ganglia  show  chromolytic  changes.  Even  the  Purkinje 
cells  of  the  cerebellum  may  be  involved  in  a  similar  manner. 

The  relation  of  the  anatomical  to  the  clinical  phenomena. — 
There  are  many  clinical  varieties  of  paralytic  dementia;  some 
are  characterised  by  profound  and  early  mental  changes,  while 
others  are  equally  remarkable  for  their  physical  disabilities. 
Most,  however,  exhibit  at  an  early  period  some  impairment  of 
the  highest  intellectual  and  moral  qualities,  a  defect  which  may 
be  correlated  with  the  changes  we  have  described  in  the  as- 
sociation systems  of  the  cerebral  cortex.  Motor  paralysis  is 
dependent  on  the  involvement  of  the  Betz  cells  of  the  pre- 
Rolandic  area,  and  on  the  consequent  degeneration  of  the 
pyramidal  tracts.  Various  transitory  phenomena,  such  as 
congestive  attacks,  epileptiform  seizures,  hemiplegias,  aphasia, 
etc.,  depend  on  irregularities  of  circulation,  and  on  the  toxic 
or  irritative  products  of  the  degenerative  process. 


SYPHILIS  OF  THE  NERVOUS  SYSTEM  159 

REFERENCES 

Good  descriptions  of  the  morbid  anatomy  of  syphilitic  diseases  of  the 
nervous  system  are  to  be  found  in  most  standard  textbooks.  The  following 
are  recommended,  and  contain  full  bibliographies: 

Allbutt  and  Rolleston:  System  of  Medicine,  vols.  vi.  and  vii.,  1910. 
CoRNiL  ET  Ranvier:  MuHuel  d'Histologie  Pathologique,  vol.  iii.     Paris,  1907, 

pp.  263-356. 
Flatau,  Minor  and  Jacobson:  Handbuch  der  path.  Anat.  des  Nervensy stems, 

1904. 
Oppenheim:  Textbook  of  Nervous  Diseases:  trans,  by  A.  Bruce,  1911. 

Recent  Articles. 

Fearnsides,  E.  G.,  Head,  H.,  McIntosh,  J.,  and  Fildes,  P.:  Brain,  1914, 

vol.  xxxvi.,  p.  I. 
Fildes,  P.,  and  McIntosh,  J.:  Brain,  1915,  vol.  xxxvii.,  pp.  141  and  401. 


CHAPTER  VI 
OTHER  INFECTIVE  DISEASES 

I.  Leprosy. 

Aetiology. — Leprosy  is  due  to  infection  of  the  tissues  of  the 
body  with  the  Bacillus  Icp.a^.  How  this  infection  occurs  is 
uncertain,  but  there  is  some  evidence  which  suggests  that  it 
comes  through  the  bite  of  bugs.  The  incubation  period  is  a 
long  one,  probably  some  months  at  least.  Having  established  a 
foothold  under  the  skin  or  mucous  membranes,  the  lepra  bacilli 
may  attack  almost  all  the  tissues  of  the  body,  but  it  is  only 
necessary  here  to  describe  their  effects  on  the  nervous  system. 

Morbid  anatomy. — The  bacilli  are  found  in  the  lepra  cells 
of  leprous  nodules.  These  are  large  connective-tissue  cells, 
varying  from  thrice  the  size  of  a  leucocyte  to  cells  of  giant  size. 
The  smaller  varieties  have  one  or  more  nuclei,  usually  eccentric ; 
the  larger  are  always  multinuclear.  Their  cytoplasm  is 
homogeneous,  and  contains  vacuoles  in  which  the  bacilli  lie 
packed  in  sheaves,  or  arranged  radially.  The  lepra  cells 
usually  occupy  the  centre  of  a  leprous  nodule,  which  is  com- 
posed of  epithelioid  and  connective-tissue  cells,  with  plasma 
and  mast  cells  in  varying  number.  These  nodules  may  be 
discrete  or  form  a  confluent  fibrous  mass  of  firm  consistency. 
In  addition  to  being  present  in  lepra  cells,  the  bacilli  may  occur 
in  rounded  clumps  suggesting  bacillary  thrombi  in  the 
lymphatics  or  the  remains  of  disintegrated  lepra  cells.  The 
number  of  bacilli  in  a  nodule  is  enormous,  and  gives  it,  at  first 
glance,  a  diffuse  red  stain  in  sections  stained  by  the  Ziehl 
Neelsen  process. 

The  nerve  trunks  are  invaded,  usually  in  their  peripheral 
portions,  by  leprous  nodules,  which  give  rise  to  an  inter- 
stitial neuritis  producing  great  thickening  of  the  nerve 
trunks  with  irregularly  spaced  fusiform  swellings  along  their 
course.  The  amount  of  paralysis  produced  is  notoriously 
at  variance   with   the   amount   of   this   thickening.     In   the 

i6o 


LEPROSY  i6i 

nodular  form  the  paralysis  and  anaesthesia  are  minimal  in 
spite  of  nerve  trunks  which  are  palpable  as  hard  irregular 
cords,  whereas  in  the  anaesthetic  form  an  advanced  degree  of 
anaesthesia  and  trophic  changes  in  the  limbs  may  be  present 
before  any  obvious  nervous  swelling.  Neisser  attributes  this 
to  a  variation  in  the  bacillus,  which,  in  the  latter  form,  seems 
to  have  a  specially  toxic  action  on  nervous  tissue.  It  is 
probable  that  in  the  majority  of  cases  the  bacilli  gain  access 
to  the  nerve  fibre  at  or  near  its  termination,  and  infiltrate 
its  sheath  from  the  point  of  access  upwards.  But  in  some 
cases  they  must  be  carried  either  by  the  blood  or  lymph  channels 
direct  to  the  upper  parts  of  the  nerve,  as  nodules  are  often 
found  there  independently  of  disease  lower  down  the  nerve, 
in  which  the  secondary  degeneration  resulting  from  the 
patch  of  interstitial  neuritis  is  the  only  obvious  change. 

Cross  section  of  the  nerves  shows  that  the  different  bundles 
of  which  the  nerve  is  composed  are  attacked  in  varying  degree. 
Some  appear  as  cords  of  fibrous  tissue  in  which  run  denuded 
axis  cylinders.  Others  are  intact  except  for  a  thick  collar  of 
connective  tissue,  which  exercises  a  certain  amount  of  pressure. 
The  myelin  tends  to  break  up,  but  may  persist  in  spite 
of  much  perineural  infiltration.  In  the  last  degree,  after  the 
leprous  nodules  have  invaded  the  interfibrillar  substance,  lepra 
bacilli  attack  the  neurolemma  sheath,  and  form  colonies  in  the 
migratory  cells  given  off  from  its  internal  surface  (p.  i6). 

The  spinal  ganglia  rank  next  to  the  peripheral  nerves  as  a 
favourite  site  of  leprous  invasion.  They  may  appear  normal, 
or  may  be  enlarged  and  sclerosed.  The  bacilli  are  most 
commonly  found  in  the  nerve  cells,  which  may  show  little 
reaction  or  may  be  enlarged  and  deformed  or  smaller  than 
normal.  The  bacilli  occupy  the  cytoplasm,  and  the  chromo- 
phil  substance  tends  to  diminish  as  the  bacilli  multiply. 

In  the  cord  the  bacilli  are  most  frequently  found  in  ventral 
horn  cells,  although  not  so  commonly  as  in  the  spinal  ganglion 
cells.  The  changes  produced  are  similar  in  the  two  forms  of 
cell.  Bacilli  have  also  been  described  in  the  peri-ependymal 
tissue.  Their  presence  in  the  cord  seems  to  give  rise  to  very 
little  reaction.  Bacilli  are  rarely  found  in  the  brain,  but  their 
presence  in  the  Gasserian  ganglion  is  not  uncommon.  They 
have  also  been  described  in  the  sympathetic  ganglion  cells. 


i62  INFECTIVE  DISEASES 

Degenerative  lesions  of  the  cord,  although  not  constant,  are 
present  in  a  large  proportion  of  cases.  These  are  confined 
to  the  dorsal  columns,  where  the  fibres  arising  in  the  root 
ganglia  of  the  limb  plexuses,  lumbo-sacral  and  cervical,  are 
chiefly  affected.  This  gives  the  dorsal  columns  in  the  upper 
cervical  region  a  tigroid  appearance  in  sections  stained  by 
Weigert's  method,  as  degenerated  bands  of  fibres  alternate 


FIG.  45. 
Leprosy  bacilli  in  a  dorsal  root  ganglion  cell. 

with  healthy  bands.  This  degeneration  may  be  due  to  in- 
vasion of  the  spinal  ganglia  by  the  bacilli  or  to  toxins  ascending 
in  the  nerve  sheaths  from  affected  nerve  trunks.  Its  relative 
frequency  and  its  histological  characteristics  seem  to  favour 
the  latter  hypothesis.  Affected  tracts  are  thinner  and  firmer 
than  normal,  and  show  some  meningeal  thickening  over  them, 
especially  near  the  entrance  of  the  dorsal  roots.  Similar 
meningeal  reaction  may  be  seen  around  the  cranial  nerves. 


ACTINOMYCOSIS  163 

2.  Streptothrix  Infection  (Actinomycosis). 

Various  members  of  the  genus  Streptothrix  attack  the 
meninges,  producing  a  suppurative  pachymeningitis,  a  diffuse 
leptomeningitis,  or  abscess  of  the  brain  or  spinal  cord. 
Usually  the  latter  are  secondary  to  disease  of  the  lungs  or  other 
organs,  but  cases  have  been  described  in  which  no  focus  of 
disease  outside  the  nervous  system  could  be  found. 

In  the  brain  the  abscess  may  arise  in  any  situation.  The  case 
where  a  small  tumour  of  the  size  of  a  hazel-nut  in  the  third 
ventricle  proved  to  be  a  thin-walled  actinomycotic  abscess  is 
probably  the  earliest  in  the  literature.  Usually  the  abscesses 
are  found  in  the  substance  of  the  cerebral  hemispheres.  They 
may  be  single  or  multiple,  and  their  walls  may  be  definite  and 
firm,  or  irregular  and  necrotic,  in  which  case  the  surrounding 
brain  substance  may  be  unhealthy  and  gelatinous.  The 
contents  of  the  abscess  are  described  as  thick,  viscous,  mucoid, 
or  oily,  and  resembling  in  colour  the  contents  of  a  compound 
cystic  ovarian  tumour.  Sometimes  the  contents  are  more 
greyish-yellow  in  colour;  they  never  resemble  ordinary  pus. 
The  odour  is  usually  foul  and  rancid.  Histologically  the  con- 
tents of  the  abscess  are  found  to  consist  mainly  of  degenerated 
polymorphonuclear  cells,  with  an  admixture  of  large  and  small 
mononuclears.  Clumps  of  the  streptothrix  are  found  towards 
the  centre  of  the  abscess.  The  walls  consist  of  brain  tissue, 
more  or  less  necrotic,  infiltrated  with  polymorpho-  and  mono- 
nuclear cells.  Around  this  is  a  zone  of  oedema,  in  which 
haemorrhages  may  have  occurred. 

3.  Tuberculosis. 

The  nervous  system  is  attacked  by  tubercular  disease  with  a 
frequency  surpassed  only  by  syphilis.  In  fact,  apart  from 
severe  epidemics  of  cerebro-spinal  meningitis  or  poliomyelitis, 
there  is  no  doubt  that  tuberculosis  is  the  most  common  infective 
disease  of  the  nervous  system  during  childhood  and  adolescence. 
There  is  no  need  to  enter  here  into  the  aetiology  of  the  disease 
or  to  discuss  the  relative  importance  of  heredity  and  environ- 
ment in  determining  its  onset;  suffice  it  to  say  that  recent 
work  is  bringing  more  and  more  into  light  the  important  part 
played  by  the  bovine  bacillus  in  causing  disease  in  the  earlier 
years  of  life. 


i64  INFECTIVE  DISEASES 

From  the  clinical  as  well  as  from  the  pathological  standpoint 
tuberculosis  of  the  central  nervous  system  divides  itself 
naturally  into  three  classes,  according  as  it  attacks  (i)  the 
cranial  bones  and  vertebrae,  and  the  dura  mater  lining  them, 
(2)  the  soft  meninges,  (3)  the  substance  of  the  brain  and  spinal 
cord.  Not  only  does  the  course  of  the  disease  differ  in  the  three 
cases,  but  the  differences  in  the  tissues,  both  as  regards  their 
texture  and  vascularity,  and  the  facilities  which  they  afford  for 
the  spread  of  the  disease,  produce  variations  in  the  minute 
pathology  of  the  process.  It  must  be  remembered,  however, 
that  in  its  essentials  tuberculosis  as  it  occurs  in  the  central 
nervous  system  differs  in  no  respect  from  the  forms  assumed 
elsewhere  in  the  body.  Here,  as  elsewhere,  we  have  the  acute 
miliary,  the  chronic  tubercular,  and  the  caseous  forms,  and 
all  possible  combinations  of  these. 

(a)  Tuberculosis  of  the  cranium,  vertebrae,  and  dura  mater.— 
Tubercular  disease  of  the  dura  mater  must  be  considered  along 
with  disease  of  the  bony  coverings  of  the  brain  and  spinal  cord, 
as  this  membrane  is  necessarily  affected  before  the  morbid 
process  can  injure  the  central  nervous  system.  Primary 
disease  of  the  dura  mater  is  rare;  in  almost  every  case  it  is 
possible  to  trace  the  disease  to  a  focus  of  osteitis  in  the 
neighbouring  bones. 

Tubercular  disease  of  the  cranium  occurs  in  the  mastoid  cells 
as  a  sequel  of  tubercular  otitis  media,  but  rarely  elsewhere. 
Here  there  is  usually  mixed  infection  with  septic  bacteria, 
and  in  default  of  surgical  intervention  the  disease  may  spread 
rapidly  inwards,  pierce  the  dura  mater,  and  produce  either 
generalised  leptomeningitis  or  abscess  of  the  brain.  Unless  the 
dura  mater  is  passed  the  disease  does  not  affect  the  central 
nervous  system,  although  it  may  produce  paralysis  of  the 
seventh  and  eighth  cranial  nerves. 

Tubercular  disease  of  the  vertebrae  (Pott's  disease)  is  common, 
and  is  a  frequent  cause  of  paraplegia.  It  is  usually  secondary 
to  disease  elsewhere  in  the  body,  but  apparently  may  be  primary. 
It  occurs  as  an  osteomyelitis  of  the  vertebrae,  commencing 
either  in  the  cancellous  tissue  of  the  body  close  to  an  inter- 
vertebral disc,  or  at  the  root  of  the  laminae.  The  vertebral 
body  may  be  considerably  eroded  before  there  is  any  evidence 
of  disease  outside  it,  and  in  such  cases  we  have  well-marked 


TUBERCULOSIS  165 

bony  deformity  with  no  sign  of  abscess  formation.  On  the  other 
hand,  an  abscess,  originating  in  a  small  focus  of  bone  disease, 
may  track  in  various  directions  and  attain  a  great  size.  All 
stages  between  these  two  extremes  may  be  present,  and  in  any 
of  them  the  spinal  cord  may  be  implicated;  but  it  is  not  often 
that  bony  deformity  alone  produces  paraplegia,  nor  is  the 
presence  of  a  psoas  or  lumbar  abscess  often  associated  with 
nervous  symptoms.  The  most  usual  cause  of  these  is  either 
an  abscess  pressing  backwards  into  the  vertebral  canal  from  a 
focus  of  caries,  or  a  tubercular  pachymeningitis. 

(i)  An  abscess  of  the  vertebral  body  may  burst  through  the 
posterior  common  ligament  and  press  directly  against  the 
anterior  surface  of  the  dura  mater.  More  frequently  it  spreads 
round  the  ligament  in  a  horseshoe  shape,  and  presses  on  the 
cord  on  its  ventro-lateral  surfaces.  In  these  cases  the  pus  is 
thick,  and  the  abscess  is  surrounded  by  a  firm  wall.  (2)  More 
commonly  without  much  liquefaction  the  tubercular  granula- 
tions fill  up  the  epidural  space  and  encircle  the  dura  mater 
more  or  less  extensively.  The  outer  layers  of  the  membrane 
become  infiltrated,  and  the  disease  spreads  up  and  down  and 
around  it,  taking  the  form  of  a  signet  ring  or  a  cuff  of  thickening. 
The  subarachnoid  space  may  be  completely  obliterated  and 
the  cord  may  be  slowly  compressed,  or  the  vascular  supply  of 
one  segment  may  be  interfered  with,  leading  to  thrombotic 
or  ischaemic  softening. 

It  is  seldom  that  the  soft  meninges  are  invaded  and  there  is 
usually  no  excess  of  lymphocytes  in  the  cerebro-spinal  fluid. 
On  the  other  hand,  it  is  not  uncommon  for  layers  of  false 
membrane  to  be  deposited  on  the  inner  surface  of  the  dura 
mater  in  the  subdural  space.  The  cord  itself  is  rarely  invaded, 
but  tubercles  may  spread  along  the  walls  of  the  vessels  into 
the  substance  of  the  cord  without  causing  a  generalised  lepto- 
meningitis. The  latter  accident  may  occur,  however,  in  which 
case  it  runs  its  usual  rapid  course. 

Occasionally  the  displacement  of  a  sequestrum  backwards 
from  a  diseased  vertebral  body  may  cause  direct  pressure  on  the 
cord,  or  a  sharp  kyphosis  may  produce  such  a  degree  of  flexion 
of  the  cord  that  the  segments  at  the  bend  are  damaged,  and 
cease  to  transmit  nervous  impulses.  Sometimes  the  amount  of 
paralysis  is  out  of  all  proportion  to  any  apparent  cause,  either 


i66  SPINAL  CARIES 

in  the  bone  or  dura  mater.  Such  cases  may  be  due  to  occlusion 
of  vessels  by  local  endarteritis.  The  nerve  roots  are  often 
implicated,  either  by  tubercular  infiltration  of  their  substance, 
or  of  the  membranes  immediately  surrounding  them,  or  by 


Fig.  46. 

Caries  of  lumbar  vertebrae.     Almost  complete  destruction  of  one  vertebral 
body,  with  granulations  invading  the  spinal  canal. 

being  compressed  between  the  laminae  when  there  is  sub- 
sidence of  the  vertebral  bodies. 

Tubercular  disease  of  the  vertebrae  usually  progresses 
favourably  and  results  in  cure,  and  there  may  be  a  corre- 
sponding improvement  in  the  nervous  symptoms,  especially 


TUBERCULAR  LEPTOMENINGITIS  167 

when  they  have  been  of  short  duration.  But  when,  in  the 
process  of  heahng,  the  kyphosis  becomes  more  marked,  a  sharp 
angle  may  be  left  against  which  the  cord  is  rubbed  and  lacerated 
by  the  movements  of  the  body.  Again,  the  cicatricial  fibrosis 
of  the  peridural  tissues  may  leave  a  tight  sleeve  around  the 
cord  which  prevents  its  recovery.  Lastly,  in  long-standing 
cases  there  may  be  such  a  degree  of  neuroglial  sclerosis  that 
only  a  very  imperfect  restoration  of  the  nerve  tracts  is  possible. 

The  condition  of  the  cord  is  similar  to  that  found  in  com- 
pression from  other  causes.  According  to  the  rapidity  of  the 
process  there  is  more  or  less  oedema,  myelin  destruction  and 
neuroglial  overgrowth.  The  axis  cylinders  frequently  persist 
in  a  remarkable  manner,  and  when  the  compression  is  relieved 
in  the  process  of  healing  the  tracts  may  resume  good  functional 
activity. 

(b)  Tubercular  leptomeningitis.  —  This  is  probably  always 
secondary  to  a  focus  of  tubercular  disease  somewhere  in  the 
body,  and  is  often  a  part  of  generalised  acute  miliary  tuber- 
culosis. In  young  children  the  primary  focus  is  commonly  a 
caseating  mediastinal  gland.  Later  in  life  it  may  be  a  tubercular 
joint  lesion  of  long  standing,  especially  where  sinuses  are 
present,  or  a  tubercular  focus  of  greater  or  less  activity  in  the 
lungs  or  abdomen.  In  a  certain  number  of  cases  the  meninges 
are  affected  by  a  direct  spread  from  caries  of  the  vertebral 
bodies. 

Although  tubercular  meningitis  is  pre-eminently  a  disease  of 
young  children,  and  shows  its  greatest  incidence  during  the 
second  year  of  life,  it  does  not  seem  to  be  due  at  all  frequently  to 
the  bovine  type  of  bacillus ;  but  more  ample  statistics  on  this 
point  are  wanted. 

Morbid  anatomj^. — On  removing  the  skull  cap  and  dura  mater 
one  is  struck  by  the  extreme  softness  of  the  brain,  which  tears 
with  the  utmost  readiness.  The  surface  is  pale;  the  arachnoid 
is  slightly  greasy  to  the  touch,  and  may  be  more  opaque  than 
normal,  and  along  the  vessels  in  the  sulci  a  few  whitish  tubercles 
may  be  seen.  The  veins  over  the  cortex  are  not  usually  dis- 
tended. The  convolutions  may  be  flattened  and  the  sulci 
somewhat  less  obvious  than  normal.  At  the  base  of  the  brain 
a  much  more  evident  exudation  is  seen.  This  may  appear  as 
a  thickening  of  the  arachnoid  of  a  greenish-grey  colour,  showing 


168  INFECTIVE  DISEASES 

numerous  tubercles  scattered  over  it  and  spread  along  the 
vessels,  or  the  base  may  be  covered  with  a  greenish  gelatinous 
exudate  which  spreads  forwards  to  cover  the  tips  of  the 
temporo-sphenoidal  lobes.  Or,  again,  the  membranes  at  the 
base  may  be  matted  into  a  dense  cream-coloured  mass,  com- 
posed of  caseating  fibrous  tissue.  The  Sylvian  fissures  are 
usually  firmly  tacked  down  by  adhesions,  and  on  separating 
the  lobes  of  the  brain  the  Sylvian  arteries  are  found  to  be 
covered  with  miliary  tubercles. 

On  section  of  the  brain  more  or  less  hydrocephalus  may  be 
apparent,  but  the  extreme  softness  of  the  brain  makes  it  very 
difiicult  to  gauge  the  amount  of  this.  The  choroid  plexus 
and  velum  interpositum  may  be  covered  with  tubercles, 
and  the  latter  is  often  bound  down  by  tubercular  adhesions. 
The  walls  of  the  ventricles,  even  where  the  ependyma 
is  intact,  are  often  extremely  soft  and  friable.  Small  areas 
of  capillary  haemorrhages  and  yellow  patches  of  softening 
may  be  found  in  the  brain  substance,  caused  by  invasion 
of  the  vessel  walls  by  the  tubercular  process.  The  dura 
mater  is  usually  healthy,  but  may  contain  a  few  small 
miliary  tubercular  nodules,  or  one  or  more  larger  caseous 
masses. 

Microscopically  the  pathological  changes  are  mainly  confined 
to  the  meninges,  where  a  varying  amount  of  exudation  is 
present.  This  may  take  the  form  of  definite  tubercles,  most 
of  which  lack  giant  cells,  or  it  may  be  more  or  less  diffusely 
spread  over  the  membranes  forming  nests  of  epithelioid  cells. 
These  usually  surround  the  smaller  vessels  and  penetrate 
through  their  walls,  eventually  filHng  up  and  blocking  their 
lumen.  The  cells  composing  these  are  mononuclear  cells  of  all 
kinds;  many  plasma  cells  and  large  macrophages  are  present, 
and  connective-tissue  cells  are  seen  proliferating  in  many  parts. 
Polymorphonuclear  cells  often  form  a  ring  round  these  nests, 
and  as  they  degenerate  are  ingested  by  the  macrophages. 
Caseation  usually  takes  place  first  in  the  centre  of  the  nodule, 
but  rarely  reaches  a  very  extreme  degree. 

The  substance  of  the  brain  and  cord  shows  little  or  no  in- 
flammatory reaction.  The  walls  of  the  vessels  show  some 
proliferation  of  the  connective  tissue  and  endothelial  cells, 
and  there   may  be  an  accumulation   of   small  cells   in   the 


TUBERCULOMATA 


169 


adventitial  lymph  spaces.  On  the  other  hand,  evidences  of 
toxic  degeneration  of  the  nervous  tissues  are  everywhere  seen. 
The  nerve  cells  show  a  varying  degree  of  degenerative  change 
and  may  be  greatly  affected.  The  axis  cylinders  also  break 
up,   and   the  brain    tissue  is   oedematous.     This   feature   of 


Fig.  47. 
Section  of  a  vessel  on  the  cerebral  cortex  the  seat  of  tubercular  arteritis. 


the  disease  is  so  marked  that  many  writers  have  termed  it 
tubercular  meningo-encephalitis. 

{c)  Tuberculomata  are  among  the  commonest  tumours  of 
the  central  nervous  system. 

In  the  hrain  they  may  occur  in  any  situation,  being  probably 
more  common  in  those  parts  which,  fill  the  posterior  cranial 


170  INFECTIVE  DISEASES 

fossa.  They  are  frequently  multiple  and  of  small  size,  varying 
from  I  to  5  mm.  in  diameter.  In  other  cases  solitary  tubercles 
of  a  larger  size,  upwards  of  i  cm.  in  diameter,  are  found. 
On  section  they  may  appear  to  blend  intimately  with  the  sur- 
rounding nervous  tissue,  or  may  be  definitely  encapsuled. 
They  are  usually  spherical  in  shape,  but  where  several  small 
tubercles  have  grown  into  one  another  the  appearance  may  be 
more  irregular.  The  outer  zone  is  usually  of  a  pinkish-grey 
colour,  and  merges  gradually  into  the  yellow  caseous  centre. 


Fig.  48. 

Photograph  of  a  section  from  the  medulla  oblongata,  showing  a  tuberculoma 
lying  dorsal  to  one  olive. 

The  surrounding  nervous  substance  may  be  obviously  softened 
or  apparently  normal,  but  the  ease  with  which  tuberculomata 
may  be  enucleated  suggests  that  some  degree  of  softening  of 
the  surrounding  tissues  is  always  present.  It  is  unusual  for 
tuberculomata  in  the  central  nervous  system  to  break  down 
and  form  abscesses ;  usually  they  do  not  go  beyond  the  stage 
of  caseation,  but  except  in  the  very  smallest  nodules  a  caseous 
centre  is  always  present. 

In  the  cord  also  they  may  be  multiple  or  single.     The  latter 


ACUTE  LEPTOMENINGITIS  171 

are  necessarily  of  smaller  size  than  in  the  brain  and  tend  to  a 
more  elongated  shape.  They  are  most  frequent  in  the  cervical 
enlargement. 

Localised  tubercular  meningo-myelitis  may  occur.  In  this 
case  the  tubercles  are  found  in  the  pia-arachnoid,  and  to  some 
extent  invading  the  cord  along  the  vessels.  For  the  most  part, 
however,  the  softening  of  the  cord  is  due,  not  to  tubercular 
infiltration,  but  to  vascular  occlusion  and  the  effects  of  tuber- 
cular toxins.  Tuberculomata  of  varying  size  may  also  be  found 
in  relation  to  the  soft  meninges  of  the  brain  without  giving  rise 
to  a  generalised  tubercular  leptomeningitis.  Their  size  and 
appearance  is  similar  to  that  of  tubercles  in  the  brain  substance. 

Microscopically  tuberculomata  of  the  central  nervous  system 
usually  show  a  caseous  centre,  which  occupies  the  greater  part 
of  the  tumour.  This  is  surrounded  by  a  zone  either  of  giant- 
celled  nodules,  or  of  infiltration  with  epithelioid  cells,  along 
with  destruction  of  the  nervous  elements.  This  forms  the 
outer  layer  of  the  tuberculoma.  Around  it  is  a  zone  which 
shows  evidence  of  toxic  degeneration  of  nerve  cells  and  fibres 
with  little  or  no  phagocytic  infiltration,  unless  we  class  under 
that  heading  the  large  number  of  granular  corpuscles  which  is 
present.  The  vessels  are  congested,  and  run  through  this  area 
into  the  outer  layer  of  the  tuberculoma,  where  they  become 
thrombosed.  It  is  sometimes  difficult  to  define  exactly  the 
boundaries  of  the  nodule,  as  the  passage  from  the  zone  of 
epithelioid  cells  to  that  of  degenerated  nervous  substance  may 
be  gradual  and  its  contour  irregular.  When,  however,  giant 
cells  are  present  they  form  a  useful  indication  of  the  outer 
strata  of  the  tuberculoma. 

4.  Acute  Leptomeningitis. 

According  as  the  inflammatory  process  attacks  chiefly  the 
pia-arachnoid  membranes  or  the  dura  mater,  the  terms  lepto- 
and  pachy-meningitis  are  used  to  denote  it.  It  is  at  first  sight 
surprising  that  in  acute  leptomeningitis  there  is  little  tendency 
for  the  disease  to  spread  outwards  and  involve  the  dura  mater. 
But  it  must  be  remembered  that  though  the  membranes  are  in 
contact  along  their  endothelial  surfaces,  there  is  no  communica- 
tion between  the  subdural  and  subarachnoid  spaces.  On  the 
other  hand,  infection  readily  spreads  from  without  inwards. 


172  INFECTIVE  DISEASES 

by  perforation  of  the  dura  mater,  and  thus  collections  of  pus 
forming  in  the  bones  of  the  skull  or  the  vertebral  column 
may  burst  through  into  the  subarachnoid  space,  and  give  rise 
to  a  generalised  leptomeningitis. 

There  are  two  main  factors  which  render  leptomeningitis 
from  any  cause  one  of  the  most  acute  and  fatal  forms  of 
infection. 

1.  We  have  to  deal  with  inflammation  in  a  space  wherein 
there  is  continual  movement  and  circulation  of  a  fluid  which 
has  minimal  antitoxic  and  bactericidal  powers  and  yet  affords 
just  sufficient  pabulum  for  the  growth  of  organisms  in  it. 
Owing  to  the  absence  of  lymph  and  the  continual  movement 
of  the  fluid,  there  is  very  little  tendency  for  inflamed  areas 
to  be  shut  off  by  adhesions;  rather  the  tendency  is  for  the 
infection  to  be  washed  from  one  place  to  another.  Conse- 
quently infection  introduced  into  any  part  of  the  subarachnoid 
area  rapidly  becomes  diffused  generally  throughout  it.  This 
is  especially  true  of  parts  below  the  tentorium  cerebelli,  as 
over  the  cerebrum  inflammatory  foci  are  frequently  limited 
by  adhesions  in  the  pia-arachnoid. 

2.  The  central  nervous  system  is  enclosed  in  a  rigid  bony 
box  which  does  not  allow  of  more  than  a  very  limited  enlarge- 
ment of  the  brain,  and  checks  any  increase  in  the  cranial 
contents.  Therefore,  when  meningeal  inflammation  raises 
the  intracranial  pressure,  the  blood  supply  to  the  brain  is 
diminished,  and  the  vital  centres,  already  poisoned  by  bacterial 
toxins,  are  deprived  of  nutrition. 

This  rise  of  intracranial  pressure  may  be  due  to  one  or  more 
of  the  following  factors: 

(i.)  Adhesions  forming  round  the  base  of  the  brain  may  shut 
off  the  escape  of  the  cerebro-spinal  fluid  from  the  cisterna 
magna  and  lead  to  an  internal  hydrocephalus.  This  is  seen 
typically  in  the  more  chronic  forms  of  meningococcal  meningitis. 

(ii.)  Obstruction  to  the  exit  of  cerebro-spinal  fluid  into  the 
general  circulation  may  be  caused  by  inflammation  and 
oedema  of  the  walls  of  the  cerebral  veins,  and  of  the  Pacchionian 
bodies,  and  by  proliferation  of  tissues  and  cells  in  the  meshes 
of  the  subarachnoid  space. 

(iii.)  The  brain  substance  itself  often  becomes  oedematous 
owing  to  the  influence  of  bacterial  poisons. 


MENINGOCOCCAL  MENINGITIS 


173 


The  causes  of   acute  leptomeningitis  may  be  classified  as 
follows:  ^ 


Primary 


r  Sporadic  type. 
Meningococcic  \  Epidemic       cerebro  -  spinal 


Secondary 


Pneumococcic 

Traumatic 

Tuberculous 

Pneumococcic 

Pyogenetic 


Other  forms 


\ 


menmgitis. 

Injuries  of  scalp,  skull,  etc. 

Tubercular  infection. 

Infection  of  ear,  nose,  orbit, 
etc. 

Pneumonia,  empyema,  en- 
docarditis, peritonitis,  etc. 

Infection  by  various  forms  of 
staphylococci  or  strepto- 
cocci derived  from  the  skin 
or  internal  organs. 

Infection  by  B.  typhosus,  coli, 
enteritidis{G2ieTtneT),dysen- 
teriae,  influenzae,  Gonococ- 
cus,  Streptothrix,  Lepto- 
thrix,  and  B.  anthracis. 


{a)  Meningococcal  meningitis  —  Aetiology. — The  meningo- 
coccus of  Weichselbaum  is  a  kidney-shaped  coccus,  occurring 
in  pairs  with  the  flattened  surfaces  opposed.  In  morphological 
characters  it  closely  resembles  the  gonococcus,  and  like  the 
latter  is  not  stained  by  Gram's  method.  Various  strains  of  the 
organism  react  differently  in  agglutinative  reactions,  and  these 
differences  are  most  marked  as  distinguishing  the  epidemic 
form  of  the  disease  from  the  chronic  posterior  basic  type  of 
Still.  Usually,  also,  the  organism  of  the  latter  disease  shows 
a  hardier  growth  in  culture.  Undoubtedly  the  organism 
is  subject  to  many  variations,  both  in  virulence  and  in 
character. 

In  the  tissues  and  exudate  it  occurs  typically  as  an  enclosure 
in  the  polymorphonuclear  cells,  and  resembles  the  gonococcus 
in  occurring  packed  in  large  numbers  in  single  cells,  while  the 
great  majority  of  leucocytes  remain  free  from  any  organisms. 
As  many  as  fifty  cocci  may  be  counted  in  a  cell  in  the  more  acute 
cases,  but  often  several  fields  must  be  searched  before  any 


174 


INFECTIVE  DISEASES 


organisms  are   found.     Cocci  are  also   found   extracellularly 
both  in  acute  and  chronic  cases. 

The  mode  of  entrance  of  the  meningococcus  to  the  subarach- 
noid space  has  been  disputed.  Some  observers  favour  the  naso- 
pharyngeal route,  and  consider  that  the  organism  finds  its  way 


Fig.  49. 

Post-basic  meningitis. 

along  the  lymphatics  surrounding  the  nasal  and  olfactory  nerves. 
Others  state  that  the  symptoms  are  usually  at  first  abdominal, 
and  that  the  organism  gains  entrance  to  the  spinal  area 
from  the  abdominal  lymphatics. 

Morbid  anatomy. — By  whichever  route  the  organism  gains 
the  meninges  the  effects  are  similar.     On  removing  the  cover- 


POST-BASIC  MENINGITIS  175 

ings  of  the  brain  the  cerebral  hemispheres  are  seen  to  be  covered 
with  a  layer  of  greenish-yellow  pus,  which  may  be  confined  to 
the  sulci  or  spread  in  a  more  even  layer  all  over  the  cortex. 
The  cortical  veins  are  greatly  distended  and  dark  in  colour. 
The  lymph  is  entirely  in  the  meshes  of  the  arachnoid  mem- 
brane, and  so  is  not  easily  washed  away  by  a  stream  of  water. 

When  the  exudation  is  more  confined  to  the  base  it  fills  the 
basal  cistern,  and  extends  downwards  over  the  pons  and 
medulla  and  forwards  over  the  poles  of  the  temporal  lobes,  but 
does  not  tend  to  spread  round  the  Sylvian  fissure  in  the  same 
way  as  that  of  tuberculous  meningitis.  On  stripping  the 
exudate  from  the  brain  cortex,  this  is  seen  to  be  firm  and  of 
almost  normal  colour.  The  convolutions  are  often  flattened 
and  the  sulci  filled  up  owing  to  internal  hydrocephalus,  and 
in  cases  of  long  duration,  especially  where  the  intracranial 
pressure  has  been  greatly  increased,  the  cortex  may  appear 
pale. 

Microscopically  the  infiltration  of  the  meninges  is  found  to 
be  practically  confined  to  the  subarachnoid  space.  Here, 
according  to  the  acuteness  of  the  infection,  we  find  an  exudate 
consisting  wholly  of  polymorphonuclear  cells,  or  of  these  with 
a  greater  or  smaller  number  of  mononuclear  cells  of  various 
types — lymphocytes,  plasma  cells,  and  macrophages.  Phago- 
cytosis is  commonly  observed.  The  polymorphonuclear  forms 
show  vacuoles  containing  organisms  or  other  debris,  and  as 
they  degenerate  are  themselves  ingested  by  the  larger  mono- 
nuclear cells. 

The  cortex  shows  very  little  inflammatory  reaction  except 
congestion  of  vessels  and  accumulation  of  small  cells  in  the 
adventitial  lymph  spaces. 

In  chronic  posterior  basic  meningitis  the  exudate  is  confined 
entirely  to  the  base,  and  consists  merely  of  a  chronic  thickening 
of  the  pia-arachnoid  membranes  in  this  area,  with  little  or  no 
lymph  exudation.  In  these  cases  hydrocephalus  forms  the 
outstanding  pathological  feature. 

(b)  Meningitis  due  to  other  pyogenic  organisms. — Menin- 
gitis due  to  other  pyogenic  organisms  gives  pathological 
appearances  similar  to  the  above — the  amount  of  exudate 
varying  with  the  acuteness  and  severity  of  the  inflammation. 
The  form  due  to  the  Bacillus  anthracis  gives  a  very  characteristic 


176  SEROUS  MENINGITIS 

picture  at  the  autopsy,  as  the  surface  of  the  brain  is  covered 
with  a  bright  red  stain  due  to  multiple  haemorrhages  into  the 
subarachnoid  space. 

The  characters  of  the  cerebro-spinal  fluid  in  meningitis  have 
already  been  discussed  (pp.  37-48).  The  pressure  is  always 
raised,  but  the  flow  may  be  retarded  by  the  thick  consistency 
of  the  fluid. 

(c)  Serous  meningitis  and  meningism. — These  terms  are  mainly 
clinical  in  significance.  They  have  been  applied  to  cases  pre- 
senting meningeal  symptoms  which  pass  off  either  rapidly 
or  gradually,  sometimes  leaving  hydrocephalus  in  their  train. 

Aetiology. — Almost  all  the  organisms  which  have  been 
mentioned  as  causing  meningitis  may  give  rise  to  the  conditions 
described  under  the  term  "  serous  meningitis,"  if  they  occur 
in  attenuated  form  or  if  the  natural  resistance  of  the  patient  is 
raised.  One  cause  may  be  the  tubercle  bacillus;  it  was  con- 
sidered until  recently  that  tubercular  meningitis  was  always 
fatal,  but  the  discovery  of  the  bacillus  in  the  spinal  fluid  of 
cases  of  mild  meningitis  which  recover  has  proved  that  this  is 
not  the  case.  A  more  common  cause  is  disease  of  the  middle  or 
internal  ear,  and  in  this  connection  it  must  be  remembered  that 
the  perilymph  of  the  internal  ear  is  in  communication  with  the 
cerebro-spinal  fluid  in  the  subarachnoid  space.  The  specific 
fevers  and  acute  pneumonia  (especially  when  the  apices  of  the 
lungs  are  infected)  may  be  accompanied  by  signs  of  meningitis. 
This  is  readily  understood  on  the  theory  of  absorption  of 
toxic  substances  along  the  spinal  nerves,  or  by  assuming  a 
meningitis  of  low  virulence. 

Morbid  anatomy. — The  post-mortem  appearances  which  have 
been  described  as  "  serous  meningitis  "  are,  for  the  most  part, 
those  of  internal  hydrocephalus,  due  to  closure  of  the  foramina 
round  the  fourth  ventricle  by  meningeal  thickening  or  by 
ependymal  adhesions.  One  ventricle  alone  may  be  dilated: 
the  lateral  when  one  foramen  of  Munro  becomes  closed,  or  the 
third  or  fourth  when  the  Sylvian  iter  is  blocked. 

Perhaps  the  term  most  appropriately  describes  the  rare  cases 
of  "  localised  serous  meningitis  "  where  meningeal  adhesions 
have  led  to  accumulations  of  fluid  over  a  limited  area  of  the 
cortex.  In  one  such  case  adhesions  between  the  upper  surface 
of  the  cerebellum  and  the  tentorium  had  dammed  back  the 


PYOGENIC  PACHYMENINGITIS  177 

fluid  in  the  posterior  cranial  fossa  and  led  to  signs  of  cerebellar 
disease.  In  other  cases  the  Rolandic  area  of  the  cortex  has  been 
compressed  by  a  cyst  of  similar  origin. 

Thrombosis  of  the  longitudinal  sinus  may  give  rise  to  a 
clinical  picture  indistinguishable  from  hydrocephalus,  but  on 
pathological  grounds  the  term  "  serous  meningitis  "  is  here 
quite  inadmissible. 

5.  Pyogenic  Pachymeningitis. 

Aetiology. — Pyogenic  infection  of  the  dura  mater  surrounding 
the  brain  or  spinal  cord  usually  occurs  secondarily  to  disease 
in  the  overlying  bones.  In  the  skull  this  commonly  occurs 
from  infection  of  the  middle  ear  or  of  the  air  sinuses, 
especially  the  mastoid  cells  and  frontal  sinus,  more  rarely 
the  ethmoidal  or  sphenoidal  cells.  It  may  also  result  from 
compound  fractures  of  the  skull.  The  causative  organisms 
most  frequently  found  are  staphylo-,  pneumo-,  and  strepto- 
cocci, and  members  of  the  B.  coli  group,  but  any  of  the  pyogenic 
organisms  may  be  responsible  either  singly  or  in  combination. 

The  dura  mater  lining  the  skull  is  extremely  resistant  to 
septic  infection,  and,  were  it  not  for  two  anatomical  char- 
acteristics, would  prove  an  impassable  barrier.  These  are 
(i)  the  presence  of  venous  sinuses.  These  communicate  on 
one  side  with  emissary  veins  running  through  the  cranium, 
and  on  the  other  with  the  veins  and  venous  lacunae  of  the 
arachnoid  membrane,  and  thus  provide  channels  whereby  septic 
processes  may  pass  through  the  dura  mater  to  the  lepto- 
meninges  and  thence  to  the  brain  itself.  In  the  case  of  the 
larger  sinuses  septic  clots  may  become  detached  and  be  carried 
to  the  heart  and  lungs.  Again,  thrombosis  of  the  superior 
longitudinal  sinus,  which  may  result  from  inflammation  of 
the  frontal  air  sinus  or  from  fractures  of  the  vertex  of  the  skull 
by  wounds  or  otherwise,  causes  congestion  and  oedema  of 
the  cortex  by  blocking  the  normal  venous  return  from  the 
cortical  vessels.  (2)  The  dura  mater  lies  between  the  resistant 
skull  and  the  less  resistant  brain  tissue.  Consequently,  when 
pus  appears  on  the  inner  side  of  the  cranium,  it  tends  to  bulge 
the  dura  mater  inwards,  and  strip  it  from  its  attachments  to  the 
cranial  bones.  When  adhesions  form  the  tension  of  the  pus 
on  the  inflamed  dura  mater  may  cause  it  to  give  way,  and  a 

12 


178  INFECTIVE  DISEASES 

communication  is  thus  formed  through  it  between  the  skull  and 
the  subdural  and  subarachnoid  spaces.  Once  the  barrier  of  the 
dura  mater  is  passed  the  inflammation  usually  finds  its  way 
rapidly  through  the  outer  layer  of  the  arachnoid  and  leads  to  a 
generalised  leptomeningitis,  to  purulent  cerebritis  or  to  abscess 
of  the  brain. 

Usually,  unless  both  these  factors  come  into  play,  i.e. 
unless  it  takes  place  in  a  region  of  the  dura  mater  whence 
emissary  veins  are  given  off  and  where  the  overlying  bone  is 
more  or  less  intact,  the  inflammatory  process  fails  to  penetrate 
the  dura  mater.  Thus,  large  abscesses  may  form  between  the 
dura  and  the  parietal  bones ;  even  over  the  frontal  and  mastoid 
regions  removal  of  the  overlying  bone  is  usually  suflicient  to 
arrest  the  progress  of  the  inflammation.  The  most  vulnerable 
region  seems  to  be  the  neighbourhood  of  the  superior  longi- 
tudinal sinus.  It  must  be  remembered  that  here  the  meningeal 
and  cortical  veins,  running  in  the  dura  and  the  arachnoid 
respectively,  pour  their  blood  into  the  sinus,  which  also 
receives  lymph  from  the  subdural  space  by  short  channels 
running  in  its  walls.  The  latter  are  in  all  probability  the 
most  common  paths  whereby  infection  passes  through  the 
dura  mater  in  this  region,  but  it  may  also  pass  along  the 
cortical  veins  from  an  infected  and  thrombosed  sinus. 

In  regard  to  the  dura  covering  the  spinal  cord  neither  of  these 
anatomical  factors  is  present.  Except  with  the  emerging  nerve 
roots  no  veins  traverse  the  membrane,  and,  laterally  and 
posteriorly  at  any  rate,  there  is  little  continuity  in  the  bony 
covering.  Even  in  the  sacrum  there  are  large  foramina 
whereby  pus  surrounding  the  theca  can  escape,  and  although 
inflammation  starting  in  the  bodies  of  the  vertebrae  may 
penetrate  the  dura  and  lead  to  leptomeningitis,  such  an  event 
is  rare  even  in  the  sacral  region  and  very  rare  elsewhere  in  the 
spine.  On  the  oth-er  hand,  an  abscess  starting  in  the  bodies 
of  the  vertebrae  may  press  the  dura  backwards  against  the 
cord,  or  may  produce  a  circular  thickening  of  the  theca,  and 
in  either  case  the  function  of  the  cord  may  be  interfered  with 
(p.  164).  Infection  through  the  spinal  theca  occurs  most 
frequently  in  bed-sores  following  lesions  of  the  spinal  cord, 
as  the  cutting  off  of  trophic  influences  renders  the  tissues  more 
vulnerable  to  septic  processes. 


ABSCESS  OF  THE  BRAIN  179 

Pyogenic  inflammation  of  the  dura  mater  differs  in  no  respect 
from  inflammation  of  a  connective-tissue  membrane  elsewhere 
in  the  body.  There  may  be  diffuse  infiltration  with  pus  cells 
but  no  macroscopic  abscess,  or  the  layers  of  the  dura  may  be 
separated  by  a  stratum  of  pus  cells;  or,  again,  the  membrane 
may  be  greatly  thickened  and  contain  small  abscesses  varying 
from  I  to  5  mm.  in  diameter.  Where  a  tunnel  has  been 
formed  through  the  dura  its  walls  are  formed  by  pus 
cells  and  granulation  tissue  with  degenerated  fibrous  tissue 
elements. 

6.  Suppurative  Encephalitis  (Abscess  of  the  Brain). 

Aetiology. — Suppurative  encephalitis  is  due  to  the  ordinary 
pyogenic  organisms,  most  frequently  the  streptococci  and 
pneumococci,  less  often  Staphylococcus  aureus,  Bacillus  coli 
and  Friedlander's  bacillus:  anaerobic  bacilli  may  also  be 
present.  Abscesses  due  to  the  tubercle  bacillus  (p.  169)  and 
streptothrix  (p.  163)  have  already  been  described. 

Abscess  of  the  brain  has  four  main  causes : 

(i)  It  may  arise  as  a  result  of  compound  fracture  of  the 
skull,  especially  when  accompanied  by  some  laceration  of  the 
brain.  This  is  a  direct  infection  of  the  brain  substance  from 
the  overlying  tissues. 

(2)  It  is  frequently  seen  as  a  result  of  acute  or  chronic 
suppuration  in  the  bones  of  the  cranium,  especially  in  otitis 
media  and  mastoiditis. 

(3)  It  is  not  uncommon  in  cases  of  purulent  bronchitis  or 
bronchiectasis. 

(4)  It  may  be  due  to  organisms  circulating  in  the  blood. 
Thus  multiple  abscesses  may  occur  in  pyaemia,  and,  less 
frequently,  so-called  "  idiopathic  "  abscess  of  the  brain  may  be 
due  to  invasions  of  the  brain  substance  by  an  organism  derived 
from  some  hidden  focus  of  inflammation  or  suppuration.  Such 
abscesses  may  arise  after  some  contusion  or  concussion  of  the 
brain,  where  there  is  no  possibility  that  the  brain  tissue  has  been 
invaded  directly  from  the  skin. 

Macroscopic  appearances. — Abscesses  of  the  brain  may 
present  different  features  according  to  their  cause.  Thus, 
abscesses  arising  from  wounds  of  the  skull  and  brain  usually 


i8o  ABSCESS  OF  THE  BRAIN 

show  a  track  of  red,  softened  brain  tissue  leading  to  the  fracture 
of  the  cranial  vault.  When  they  occur  around  some  foreign 
body,  such  as  a  splinter  of  bone,  a  fragment  of  shell  or  bomb- 
casing,  or  a  bullet,  there  may  be  an  open  track  surrounded  by 
bruised  brain  tissue.  In  some  cases  the  foreign  body,  as 
it  passes  through  the  brain,  leaves  septic  material  behind 
it,  and  an  abscess  results  in  the  middle  of  the  track,  while 
the  foreign  body  itself  lies  at  the  end  of  the  track  surrounded 
by  healthy  brain  tissue. 

In  wounds  of  the  brain  it  is  common  enough  to  find  a  chain 
of  abscesses  of  diminishing  size  apparently  separate  from  one 
another,  but  connected  by  a  zone  of  hyperaemic  brain  tissue, 
and  the  difference  in  thickness  and  firmness  of  the  capsules 
of  these  abscesses  gives  an  indication  as  to  their  relative  age. 
Such  abscesses  may  be  of  any  shape :  when  formed  in  the  track 
of  a  foreign  body  they  tend  to  run  along  the  track;  not  in- 
frequently they  are  rounded,  especially  in  the  more  chronic 
cases,  but  they  may  have  numerous  finger-like  extensions 
separated  by  spurs  or  bands  of  firm  tissue. 

The  limiting  wall  also  varies  considerably.  In  some, 
especially  in  the  earlier  stages,  it  is  irregular  and  indefinite, 
apparently  consisting  merely  of  haemorrhagic  and  softened 
brain  tissue.  In  others,  which  are  older,  the  wall  is  thick 
and  firm,  and  yellowish  in  colour,  and  may  strip  with  the 
greatest  ease  from  the  softened  brain  tissue  surrounding 
it,  so  that  the  abscess  may  be  enucleated  without  rupture. 

Abscesses  resulting  from  mastoiditis  are  usually  found  in  the 
temporal  lobe  or  in  the  cerebellar  hemisphere  on  the  same  side 
as  the  ear  disease ;  but  they  may  occur  on  the  opposite  side  of 
the  brain,  probably  as  a  result  of  the  infection  having  spread 
along  the  petrosal  sinuses  or  the  lymphatics.  Usually  there  is 
evidence  of  disease  of  the  dura  mater,  and  a  track  of  hyperaemic 
brain  tissue  joins  the  abscess  with  the  meninges.  But  in  other 
cases  it  is  not  possible  to  trace  any  connection  of  the  abscess 
with  the  surface  of  the  brain.  These  abscesses  may  become 
chronic  and  attain  a  large  size:  they  are  usually  single  and 
rounded,  but  may  be  multiple. 

Abscesses  of  the  brain  arising  in  the  course  of  chronic 
lung  disease  are  usually  single  and  are  most  often  found 
in  the  left  cerebral  hemisphere,  but  they  may  occur  anywhere 


Fig.  50. 

Right  tempovo- sphenoidal  abscess  secondary  to  middle-ear  disease. 


Fig.  51. 
Bilateral  abscesses  in  frontal  lobes  secondary  to  sphenoidal  sinusitis. 


Fig.  52. 

Cavity  in  left  cerebellar  lobe,  the  result  of  an  abscess  secondary  to  middle. 

ear  disease. 


i82  INFECTIVE  DISEASES 

in  the  brain,  cerebellum  or  brain-stem.  The  pus  is  frequently 
foetid. 

The  evolution  of  abscess  from  acute  encephalitis  may  be 
divided  into  three  stages : 

(i)  A  stage  resembling  acute  encephalitis,  in  which  there 
appear  areas  of  softening  and  liquefaction. 

(2)  These  areas  enlarge,  merge  into  one  another,  and  tend  to 
lose  their  red  colour;  fully  formed  pus  makes  its  appearance, 
at  first  in  minute  drops. 

(3)  In  the  third  stage  the  reaction  in  the  surrounding  brain 
tissue  limits  the  abscess,  a  definite  wall  is  formed,  and  the 
surrounding  encephalitis  subsides.  This  stage  may  never  be 
reached,  and  the  encephalitis  may  continue  its  spread  until 
the  death  of  the  patient. 

The  pus  of  a  cerebral  abscess  is  usually  yellowish  and  creamy, 
but  may  have  a  reddish  or  greenish  tinge.  Although  in  most 
cases  it  is  odourless  it  may  be  extremely  offensive,  and  where 
anaerobic  bacilli  are  present  it  has  a  characteristic  acrid  smell. 

Microscopic  appearances. — From  within  outwards  the  walls 
of  a  brain  abscess  consist  of : 

(i)  A  layer  of  pus  cells,  mainly  degenerated  polymorpho- 
nuclear leucocytes,  with  an  admixture  of  larger  cells  with 
pyknotic  nuclei  and  granular  cytoplasm  which  may  contain 
fatty  substances.  Calcification  may  be  present  in  this  layer, 
sometimes  forming  a  ring  near  its  junction  with  the  layer 
next  outside  it.  (2)  Granulation  tissue  in  process  of  organi- 
sation. Connective-tissue  fibres  form  a  large  part  of  its 
structure,  and  small  blood  vessels  with  relatively  abundant 
fibrous  tissue  in  their  walls  are  plentiful,  both  these  structures 
tending  to  lie  parallel  to  the  wall.  It  is  obvious  that  the 
fibrous  tissue  arises  from  the  walls  of  the  vessels,  around  which 
it  is  especially  dense.  Few  glia  cells  or  fibres  are  present  in 
this  layer,  but  in  the  earlier  stages  there  are  numerous  fat- 
containing  phagocytic  cells  (compound  granular  corpuscles). 
It  is  by  this  layer  that  the  abscess  is  limited,  and  it  eventually 
forms  the  firm  wall  of  a  chronic  abscess.  (3)  The  zone  of 
glial  reaction.  Here  the  fibrous  tissue  is  confined  to  the 
walls  of  the  blood  vessels,  round  which  it  forms  a  much 
thicker  sheath  than  in  healthy  brain  tissue.  In  recent  abscesses 
there  is  dilatation  of  the  vessels  and  proliferative  activity  of 


ABSCESS  OF  THE  BRAIN 


183 


their  walls,  with  swelling  and  multiplication  of  the  lining 
endothelial  cells  and  the  formation  of  numerous  new  capillaries. 
The  adventitial  sheaths  of  the  larger  vessels  for  a  considerable 
distance  from  the  abscess  wall  are  distended  with  small  round 
cells,  plasma  cells,  and  polymorphonuclear  leucocytes.  The 
glia  cells  show  the  various  changes  common  to  all  forms  of 
glial  reaction.  Everywhere  they  are  increased  in  number, 
and  there  may  be  many  large,  globular  "  amoeboid  "  forms 
and  elongated  giant  cells,  with  terminal  fibres  arranged  parallel 


Ai 


A*v^ 


.  •*•-*•:  ,Y, 


*-T 


>.» « »  J 

•■.•■-  /■>>    .'.••'•  •:".■  •-" "  '../rr^^-tr^'MP 

Fig.  53. 

Section  from  the  wall  of  a  cerebral  abscess,  showing  the  formation  of  fibrous 
tissue  and  numerous  granular  corpuscles. 

to  the  abscess  wall.  The  amount  and  character  of  the  glial 
reaction  varies  according  to  the  state  of  encapsulation  and  age 
of  the  abscess.  It  does  not  begin  to  be  apparent  until  the  third 
week.  Eventually  the  reaction  settles  down  into  a  gliosis  of 
which  fine  glial  fibres  form  the  basis,  with  numerous  small 
glial  nuclei  scattered  along  them. 

The  neighbouring  nerve  cells  are  always  damaged  to  some 
extent.  There  is  a  powdery  condition  of  the  Nissl  granules 
or  a  diffuse  staining  of  the  cell  body. 


i84  ABSCESS  OF  THE  SPINAL  CORD 

Suppurative  Myelitis  (Abscess  of  the  Cord). 

Aetiology. — This  rare  condition  may  be  due  to  causes  similar 
to  those  of  abscess  of  the  brain,  and  most  often  arises  in 
pyaemia  or  in  the  course  of  chronic  suppurative  disease  of  the 
lungs  or  of  the  genito-urinary  tract.  It  may  also  be  due  to 
direct  spread  of  infection  in  wounds  of  the  spine. 

Abscesses  of  the  cord  are  usually  solitary,  but  may  be  multiple. 
They  tend  to  affect  the  centre  of  the  cord,  especially  the  grey 
matter,  and  to  run  up  and  down  the  cord  in  the  form  of  a 
spindle,  often  causing  much  distension.  This  appears  to 
be  due  to  the  firmness  of  the  surrounding  pia  mater,  which 
limits  the  outward  growth  of  the  abscess  and  makes  it  seek 
a  line  of  less  resistance  in  the  long  axis  of  the  cord.  The 
abscess  may  have  definite  walls,  or  it  may  consist  merely  of 
a  pale  purulent  centre  in  a  red  area  of  acute  myelitis.  It  is 
often  surrounded  by  a  zone  of  suppurative  meningitis. 

The  microscopic  appearances  differ  little  from  those  described 
above  in  reference  to  abscess  of  the  brain.  Owing  to  the 
tendency  to  spread  longitudinally  there  is  less  encapsulation 
by  fibrous  tissue. 

7.  Acute  Myelitis. 

The  only  scientific  classification  of  various  forms  of  acute 
myelitis  would  depend  upon  their  bacteriology.  In  the  present 
state  of  our  knowledge,  however,  the  bacteriology  of  acute 
myelitis  is  not  sufficiently  advanced  to  allow  of  a  definite 
classification  on  that  basis,  and  it  is  wiser  to  divide  the  forms 
of  myelitis  into  those  which  are  due  to  organisms  of  a  non- 
syphilitic  nature  and  those  which  are  brought  about  by  the 
action  of  the  Treponema  pallidum.  It  is  convenient  to  call 
the  former  class  acute  infective  myelitis  and  the  latter  syphilitic 
myelitis  (p.  141),  and  it  should  be  realised  at  once  that  the 
latter  includes  probably  80  per  cent,  of  all  cases. 

Infective  myelitis. — This  is  a  comparatively  rare  disease 
having  no  definite  relation  to  age  or  sex,  although  young  adults 
are  probably  its  most  common  victims.  It  differs  from  acute 
poliomyelitis  in  presenting  no  epidemic  form  and  having  no 
associations  with  special  climates  or  special  seasons.  The 
aetiological  value  of  trauma,  chills,  strains,  or  various  excesses 


ACUTE  MYELITIS  185 

cannot  be  highly  estimated,  although  some  of  these  factors 
may  have  a  predisposing  influence.  The  acute  specific  fevers 
appear  to  have  a  more  intimate  relationship  with  the  disease, 
and  a  number  of  cases  have  been  recorded  in  which  the 
onset  of  the  spinal  symptoms  has  occurred  in  the  course  or  in 
the  sequel  of  measles,  smallpox,  typhoid  fever,  and  gonorrhoea. 
It  must  not  be  too  hastily  assumed  that  in  such  cases  the 
infective  agent  of  the  fever  and  that  of  the  myelitis  has  always 
been  identical,  but  some  observers  hold  the  view  that  a  specific 
typhoid  myelitis  for  which  the  typhoid  bacilli  are  actively 
responsible  should  be  recognised.  No  other  aetiological  factor 
has  attracted  special  attention,  but  the  association  of  certain 
forms  of  myelitis  with  pregnancy  or  the  puerperium  has  been 
noted  in  several  instances,  and  a  toxic  myelitis  with  relapsing 
features  has  been  described  in  this  connection. 

Pathogenesis. — It  is  to  be  presumed  that  an  infective  myelitis 
can  arise  in  one  or  other  of  the  following  ways : 

(i)  As  an  extension  from  inflammatory  processes  involving 
neighbouring  tissues,  such  as  the  meninges  or  the  vertebral 
column.  An  example  of  this  process  is  afforded  by  the  tuber- 
cular form  of  myelitis  which  occurs  as  a  secondary  complica- 
tion in  cases  of  spinal  caries  or  of  tubercular  meningitis. 
Similar  forms  of  myelitis  are  often  present  in  some  degree  in 
cases  of  meningitis  due  to  various  other  organisms,  such  as  the 
pneumococcus,  staphylococcus,  streptococcus,  etc.  This  may 
not  be  evident  on  the  clinical  side,  as  the  symptoms  of  myelitis 
are  often  overshadowed  by  those  of  the  meningeal  affection. 

(2)  As  the  result  of  an  infection  of  the  spinal  marrow  through 
the  blood  stream.  This  may  occur  in  the  course  of  a  general 
pyaemia,  or  possibly  as  a  purely  local  phenomenon  when  the 
circulating  virus  affects  the  spinal  cord  alone. 

(3)  As  the  result  of  an  infection  through  the  lymphatic 
system.  It  has  been  shown  experimentally  that  infection  of 
the  spinal  cord  may  take  place  along  the  course  of  the  lymphatic 
vessels  which  accompany  the  spinal  nerves  and  spinal  roots, 
and  that  such  an  infection  may  give  rise  to  an  infective  myelitis 
similar  to  the  disease  which  is  met  with  in  human  beings. 
It  is  probable  that  some  cases  of  infective  myelitis  which  occur 
in  association  with  septic  processes  of  the  pelvic,  abdominal  or 
thoracic  organs  are  to  be  explained  on  these  lines. 


i86  INFECTIVE  DISEASES 

The  bacteriology  of  infective  myelitis  is  only  in  its  in- 
fancy, its  progress  being  hampered  by  the  fact  that  many 
organisms  appear  to  be  very  short-lived  in  the  spinal  tissues, 
and  also  by  the  fact  that  secondary  infections  may  sometimes 
lead  to  wrong  conclusions.  The  ordinary  pyogenic  organisms 
have  been  cultivated  from  the  spinal  cord  in  fatal  cases  of  the 
disease,  and  occasionally  organisms  which  are  less  familiar  have 
been  recovered  in  a  similar  way. 

Morbid  anatomy. — It  has  been  customary  to  describe  various 
forms  of  myelitis  as  transverse,  diffuse  or  disseminated,  accord- 
ing to  the  distribution  of  the  morbid  process  in  the  cord,  although 
the  actual  character  of  the  lesion  is  similar  in  most  cases.  For 
instance,  a  myelitis  which  is  limited  to  one,  two,  three,  or  at 
most  four  segments,  and  which  affects  the  transverse  area  of 
the  cord  within  these  limits  more  or  less  completely,  is  usually 
called  a  transverse  myelitis.  A  diffuse  myelitis  involves  a 
considerable  length  of  the  spinal  marrow  without  definite 
interruption,  and  is  often  found  when  the  clinical  symptoms 
have  suggested  an  ascending  process.  A  case  of  this  kind  is 
clinically  termed  an  acute  ascending  myelitis.  Disseminated 
myelitis  implies  the  presence  of  two  or  more  foci  of  the  disease 
separated  by  comparatively  healthy  tissue. 

The  macroscopical  appearances  vary,  of  course,  with  the 
length  of  time  which  has  elapsed  since  the  onset  of  the  disease. 
In  early  cases  the  areas  involved  are  softer  than  normal, 
sometimes  almost  diffluent,  swollen,  oedematous  and  generally 
hyperaemic.  Haemorrhages  may  be  present  and  give  a  dark 
red  or  brown  colour  to  the  tissues.  The  most  noticeable 
feature  upon  making  a  transverse  section  through  an  area  of 
myelitis  is  the  absence  of  any  definition  between  the  white  and 
grey  substances.  The  soft  meninges  usually  present  dilated 
blood  vessels  and  sometimes  afford  evidence  of  serous  or 
purulent  inflammation.  The  exudation  is  generally  more  pro- 
fuse on  the  posterior  than  on  the  anterior  aspects  of  the  cord. 
In  cases  which  are  of  longer  standing  the  tissues  are  more 
shrunken  and  less  vascular,  although  they  may  present  some 
mottling  with  old  blood  pigment.  Sections  through  the  cord  at 
levels  distant  from  the  seat  of  inflammation  may  show  secondary 
degenerations  in  the  ascending  and  descending  tracts  of  the 
white  columns.     At  a  still  later  period  the  diseased  area  is  of 


ACUTE  MYELITIS  187 

firmer  consistence,  and  transverse  sections  may  reveal  the 
presence  of  one  or  more  cysts. 

When  sections  of  the  cord  have  been  cut  and  stained  by 
suitable  methods,  the  morbid  changes  are  seen  under  the 
microscope  to  involve  the  blood  vessels,  the  neuroglia,  the 
nervous  tissues  and  the  meninges. 

All  the  hlood  vessels  of  the  affected  area,  small  and  large, 
show  marked  engorgement,  and  many  of  them  are  surrounded 
by  large  masses  of  nucleated  cells  partly  crowded  in  the  meshes 
of  their  adventitial  sheaths  and  partly  in  the  surrounding 
tissues.  These  nucleated  cells  include  lymphocytes,  plasma 
cells,  mast  cells  and  polymorphonuclear  leucocytes  in  varying 
numbers.  The  proportion  of  leucocytes  to  other  cells  appears 
to  vary  considerably  and  to  depend  upon  factors  which  are 
still  obscure.  In  Marchi-stained  sections  many  cells  filled  with 
fatty  granules  may  be  detected  in  and  around  the  walls  of  the 
blood  vessels.  Thrombosis  is  occasionally  met  with,  and 
haemorrhages  into  the  tissues  are  frequent.  The  neuroglia 
shows  evidence  of  oedema  in  the  shape  of  spaces  which  are 
either  empty  or  filled  with  an  amorphous  granular  material, 
deposited  in  the  process  of  fixation  from  the  albuminous  fluid 
in  which  the  tissues  have  been  bathed.  The  neuroglial  cells 
are  often  swollen  and  sometimes  vacuolated.  Their  nuclei 
have  undergone  multiplication  and  their  processes  are  often 
lost.  They  are  probably  much  increased  in  number,  especially 
in  the  neighbourhood  of  the  dilated  vessels  and  their  lymphatics. 
The  nerve  cells  of  the  grey  matter  become  swollen,  rounded 
and  homogeneous  in  appearance.  The  chromatin  granules 
disappear,  and  the  nuclei  are  displaced  from  their  central 
position  and  may  often  protrude  from  the  surface  of  the  cell. 
The  axis  cylinder  processes  are  swollen  and  sometimes  broken. 
In  some  parts  the  nerve  cells  may  have  disappeared  altogether. 
The  chief  changes  in  the  white  matter  are  those  which  affect 
the  myelin  sheaths.  These  become  swollen  and  varicose, 
and  rapidly  lose  their  power  of  staining  by  the  Weigert-Pal 
method.  The  Marchi  method  reveals  the  presence  of  fatty 
changes  in  the  form  of  darkly  stained  globules  of  irregular  size 
and  shape.  The  axis  cylinders  are  often  swollen  and  irregular 
in  outline.  When  the  myelin  has  disappeared  the  axis  cylinders 
may   remain   unsupported,   with   the   result   that   a   rarefied 


i88  INFECTIVE  DISEASES 

appearance  is  given  to  some  areas.  The  meninges  show  dilated 
blood  vessels  and  a  cellular  infiltration  of  the  pial  tissues  and 
of  the  vessel  walls. 

If  the  spinal  cord  is  examined,  by  the  Marchi  method,  at  a 
period  of  two  or  three  weeks  after  the  onset  of  the  disease, 
it  will  be  seen  that  much  of  the  fat  which  results  from  myelin 
degeneration  has  been  taken  up  by  large  granular  cells  which 
are  probably  of  neuroglial  origin.  Sections  through  other 
levels  of  the  cord  display  in  a  striking  manner  the  ascending 
and  descending  degeneration  in  the  white  columns.  Still  later 
these  degenerations  are  only  visible  when  the  Weigert-Pal 
method  is  used.  By  this  time  the  vessels  have  ceased  to  show 
such  marked  cellular  infiltration,  and  their  walls  are  thickened 
and  perhaps  hyaline  in  appearance.  Neuroglial  sclerosis  is 
evident  in  parts  from  which  the  nervous  elements  have  disap- 
peared, and  such  areas  may  show  an  increase  in  the  number  of 
blood  vessels.  Secondary  degeneration  may  also  be  found 
in  the  ventral  roots  and  in  the  efferent  fibres  of  the  peripheral 
nerves  coming  from  levels  at  which  the  grey  matter  has  been 
seriously  affected. 

8.  Tetanus. 

Tetanus  is  a  disease  produced  by  the  exotoxins  of  a  specific 
micro-organism,  the  tetanus  bacillus,  which  have  a  powerful 
action  on  the  motor  cells  of  the  central  nervous  system. 
Tetanus  bacilli  usually  gain  access  to  the  body  through  a 
wound  or  scratch  of  the  skin,  especially  when  this  is  contaminated 
with  street  dust  or  highly  manured  soil.  The  tetanus  bacillus 
is  a  common  saprophyte  of  the  intestines  of  horses,  and  is 
therefore  spread  mostly  through  the  medium  of  road  sweepings 
and  horse  manure.  It  is  very  pathogenic  to  horses  as  well  as  to 
man,  and  causes  many  deaths  among  new-born  foals. 

Experimental  work  has  shown  that  if  washed  spore-free 
tetanus  bacilli  are  injected  under  the  skin  no  tetanic  symptoms 
result,  but  if  suppuration  is  brought  about  by  injecting  other 
pyogenetic  organisms  along  with  them,  or  if  their  entrance  is 
accompanied  by  mechanical  irritants,  such  as  a  splinter  of  wood, 
the  bacilli  multiply  in  the  wound  and  give  rise  to  the  disease. 
This  has  borne  out  the  clinical  facts  that  tetanus  rarely  results 
from  a  clean  wound,  but  if  suppuration  ensues,  and  still  more 


TETANUS  189 

if  there  is  any  splintering  of  neighbouring  bones,  tetanus  is 
very  liable  to  occur. 

The  bacilli  themselves  remain  localised  to  the  site  of  infection, 
and  seem  to  have  no  power  of  migration,  but  the  exotoxins 
formed  by  them  diffuse  out  into  the  tissues  and  reach   the 
central  nervous  system,  on  which  they  have  a  selective  action. 
Much  work  has  been  done  on  the  paths  by  which  this  is  reached. 
It  was  shown  in  1902  by  Marie  and  Morax,  and  a  year  later 
by  Meyer  and  Ransome,  that  the  chief  path  is  along  the  nerves 
of  the  affected  limb,  and  it  was  thought  by  them  that  the  toxins 
passed  chiefly  up  the  axis  cylinders,  which  were  reached  by  the 
motor  end-plates  of  the  muscles  of  the  limb.     Passing  thence 
to  the  motor  cells  of  the  ventral  horn  of  the  same  side,  the 
toxins  were  considered  to  spread  up  and  down  the  cord  either 
by  lymphatic  channels  or  along  axis  cylinders  to  the  cells 
supplying  the  other  limbs  and  the  cranial  nerve  nuclei.     They 
showed  that  tetanus  toxin  injected  into  the  muscles  of  a  limb 
passed  rapidly  into  the  nerve,  so  that  an  hour  after  the  injection 
it  could  already  be  demonstrated  by  injection  of  emulsions  of  the 
nerve  into  smaller  animals.     Section  of  the  nerve  of  the  injected 
limb  prevented  the  toxin  spreading  directly  to  the  nervous 
system  and  made  its  action  weaker  and  more  diffuse.     Section 
of  the  cord  after  injection  of  toxin  into  a  hind-limb  prevented 
the  spread  of  symptoms  to  the  fore-limb  and  head.     They  also 
showed  that  the  latent  period  between  the  injection  of  the 
toxin  and  the  resulting  symptoms  varied  directly  with  the  size  of 
the  animal — that  is,  with  the  distance  which  had  to  be  travelled 
by  the  toxin.     They  found  that  whereas  maximal  effects  are 
obtained  by  injection  of  tetanus  toxin  into  a  motor  nerve, 
minimal  effects  result  when  it  is  injected  into  a  purely  sensory 
nerve,  such  as  the  infra-orbital.     This  anomaly  has  been  ex- 
plained by  the  more  recent  work  of  Teale  and  Embleton. 

When  toxin  is  injected  into  the  spinal  cord  or  into  a  dorsal 
root  between  the  ganglion  and  the  cord  there  is  evidence  of 
hyperaesthesia  and  paroxysmal  hyperalgesia  in  the  correspond- 
ing segmental  area.  This  has  been  called  "  tetanus  dolorosus." 
Direct  injection  of  the  toxin  into  the  brain  does  not  produce 
the  ordinary  tetanic  symptoms,  but  causes  psychical  irritability 
and  epileptiform  convulsions  and  is  rapidly  fatal  (cerebral 
tetanus).     The  minimal  fatal  dose  in  this  case  is  very  much 


190  INFECTIVE  DISEASES 

smaller  and  the  incubation  period  much  shorter  than  with 
subcutaneous  injection.  It  has  been  shown  by  Wassermann 
and  Takaki  that  emulsion  of  brain  of  a  susceptible  animal 
can  neutralise  tetanus  toxin  so  that  injection  of  the  supernatant 
fluid  from  a  mixture  of  these  two  produces  no  evil  effects. 
It  was  suggested  at  first  that  this  was  due  to  the  formation  of 
antibodies  by  the  cells  of  the  central  nervous  system,  but  it 
seems  more  likely  that,  as  Roux  and  Borrell  suggested,  this 
is  an  adsorption  phenomenon  or  loose  chemical  union  between 
the  brain  substance  and  the  toxin. 

The  experiments  on  the  effects  of  antitoxin  have  afforded 
confirmatory  evidence  of  the  selective  affinity  of  the  toxin  for 
the  nervous  system;  thus  death  results  after  the  injection  of 
a  fatal  dose  of  toxin  directly  into  the  sciatic  nerve  of  an  animal, 
even  when  a  dose  of  antitoxin,  sufficient  to  neutralise  it,  has 
previously  been  injected  by  the  intravenous  or  subcutaneous 
route.  Further,  the  injection  of  antitoxin  into  the  main  nerve 
of  the  limb  will  prevent  the  effects  of  a  previous  dose  of  toxin 
spreading  to  the  cord  at  a  period  after  the  injection  when  a 
similar  dose  injected  intravenously  would  have  had  little  or  no 
effect.  It  seems  likely  that  antitoxin  circulating  in  the  blood, 
whether  introduced  by  injection  or  formed  by  the  cells  of  the 
animal,  has  only  power  to  neutralise  that  part  of  the  tetanus 
toxin  which  is  not  already  fixed  by  the  tissues  of  the  nervous 
system. 

Additional  light  has  recently  been  shed  on  the  paths  of 
spread  of  tetanus  toxin  and  the  action  of  antitoxin  by  the  work 
of  Teale  and  Embleton.  These  authors  confirmed  the  earlier 
work,  which  showed  that  tetanus  toxin  spread  directly  up  the 
motor  nerves  to  the  cells  of  the  ventral  cornua.  They  found, 
however,  that  the  injection  into  the  nerve  of  foreign  colloids, 
such  as  horse  serum  and  egg  albumen,  have  an  exactly  similar 
action  to  tetanus  antitoxin  in  blocking  the  spread  of  toxin  up 
the  nerve.  They  concluded,  therefore,  that  the  toxin  spread 
chiefly  up  the  neural  lymphatics,  and  that  this  action  of 
tetanus  antitoxin  is  not  wholly  specific,  but  due  partly  to  its 
colloidal  nature.  Other  methods  of  temporarily  closing  the 
neural  lymphatics,  such  as  injecting  iodine  into  the  nerve  ten 
days  before  the  injection  of  toxin,  had  the  same  blocking  effect. 

They  found  that  the  reason  why  tetanus  toxin  does  not 


TETANUS  191 

spread  to  the  cord  by  the  dorsal  roots  and  so  produce  tetanus 
dolorosus  was  that  the  dorsal  root  ganglion  has  a  definite 
filtering  or  blocking  action  on  toxins,  as  well  as  on  other  colloid 
substances,  such  as  trypan  blue.  When  the  latter  was  injected 
into  a  nerve  it  could  be  traced  as  far  as  the  dorsal  root  ganglion, 
but  not  beyond  it  to  the  dorsal  root,  whereas  it  was  seen  to 
spread  to  the  ventral  surface  of  the  cord  along  the  ventral  root. 
It  was  also  found  that  when  all  the  ventral  roots  of  a 
hind-limb  were  cut  before  tetanus  toxin  was  injected  into 
the  corresponding  sciatic  nerve  no  symptoms  resulted  from 
the  injection. 

Meyer  and  Ransome  had  previously  shown  that  the  injection 
of  tetanus  antitoxin  into  a  sciatic  nerve  protected  that  limb 
from  involvement  in  the  general  spasms  produced  by  intra- 
venous injection  of  tetanus  toxin.  This  was  thought  to  be  due 
to  spread  of  the  antitoxin  to  the  cells  of  the  ventral  horn. 
Teale  and  Embleton,  however,  showed  that  the  same  pro- 
tective action  is  exerted  by  egg  albumen,  and  must  be  due 
in  that  case  simply  to  a  blocking  of  the  neural  lymphatics. 
This,  in  their  view,  is  strong  evidence  that  although  some  of 
the  toxin  may  spread  in  the  cord,  the  greater  part  of  that 
which  affects  other  parts  of  the  cord  and  brain-stem  reaches 
them  along  the  motor  nerves  arising  there.  They  also  came 
to  the  conclusion  as  a  result  of  their  experiments  that  a  foreign 
protein,  such  as  tetanus  antitoxin,  could  not  pass  into  the 
tissues  of  the  brain  and  cord  if  injected  either  into  the  general 
circulation  or  into  the  subarachnoid  space,  a  conclusion  which, 
if  confirmed,  is  of  very  far-reaching  importance. 

The  clinical  features  of  the  disease  as  observed  in  man 
bear  out  these  conclusions.  In  the  first  place,  tetanus  fre- 
quently remains  limited  to  the  affected  limb  when  a  prophylactic 
dose  of  antitoxin  has  been  given,  and  as  a  general  rule  the  onset 
of  tetanus  is  heralded  by  spasms  limited  to  the  wounded  limb. 
In  the  natural  disease  the  conditions  are  somewhat  different 
from  those  produced  by  the  injection  of  tetanus  toxin,  as  the 
tetanus  bacilli  in  the  wound  continue  to  elaborate  toxins,  and 
therefore  the  intravenous  injection  of  antitoxin  will  be  of 
some  use  in  all  stages  of  the  disease,  but  it  has  been  shown 
that  it  has  little  effect  in  modifying  the  course  of  the  disease 
once  tetanic  symptoms  have  shown  themselves.    .Intrathecal 


192  INFECTIVE  DISEASES 

injection  has  been  thought  to  be  more  efficacious;  but  if  the 
rapidity  with  which  foreign  substances  disappear  from  the 
subarachnoid  space,  and  the  hmited  relations  between  this 
space  and  the  lymphatics  of  the  cord  are  taken  into  account, 
it  seems  unlikely  that  the  passage  of  the  toxin  up  the  cord 
would  be  arrested  by  such  measures. 

A  form  of  tetanus  has  been  observed  resulting  from  wounds 
of  the  face,  in  which  there  is  more  or  less  complete  paralysis  of 
the  facial  nerve.  A  similar  paralysis  may  affect  the  ocular 
muscles  in  wounds  of  the  orbit  and  globe.  While  the  paralysis 
is  usually  unilateral,  it  may  be  bilateral  or  affect  only  the 
opposite  side  to  the  lesion.  The  pathology  of  such  cases  is 
doubtful,  and  it  is  possible  that  a  peripheral  neuritis  of  septic 
origin  plays  some  part  in  them,  though  their  absence  in  ordinary 
septic  wounds  of  the  face  renders  this  very  doubtful.  It  is 
more  likely  that  they  are  direct  effects  of  the  tetanus  toxin 
which,  passing  up  the  motor  filaments,  comes  very  rapidly 
into  contact  with  the  cells  of  the  seventh  and  third  cranial 
nuclei.  It  is  likely  that  a  similar  paralytic  effect  occurs 
sometimes  in  the  limbs,  but  as  only  a  small  proportion  of  the 
motor  nerve  cells  are  affected,  the  resulting  paralysis  is  apt 
to  be  obscured  by  the  tetanic  spasm  of  other  muscles. 

Splanchnic  tetanus  affecting  the  involuntary  muscles  has 
been  described  as  occurring  after  wounds  of  the  thorax  and 
abdomen,  and  is  supposed  to  be  due  to  absorption  of  tetanus 
toxins  along  the  sympathetic  nerves. 

The  histological  changes  in  the  nervous  system  in  tetanus 
have  no  definite  characteristics.  Some  degree  of  interstitial 
neuritis  in  the  nerves  connected  with  the  wound  is  frequently 
found,  but  this  has  more  relationship  to  the  presence  of  pyogenic 
organisms  than  to  the  tetanus  bacillus.  Various  changes  have 
been  described  in  the  cells  of  the  nervous  system,  particularly 
those  of  the  motor  cortex.  These  consist  in  perinuclear 
chromatolysis  and  pallor  of  the  cell  body  at  the  origin  of  the 
axon,  going  on  to  swelling  of  the  cell  body  and  alteration  of  its 
contour.  It  has  been  shown,  however,  that  these  appearances 
have  no  definite  relation  to  the  disease,  as  they  occur  on  both 
sides  of  the  cord  when  the  symptoms  are  unilateral,  and  may 
be  more  intense  when  the  severity  of  the  symptoms  has 
diminished.     There  is  usually  hyperaemia  of  various  areas  in 


ACUTE  POLIOMYELITIS  193 

the  central  nervous  system,  in  both  the  white  and  grey  matter. 
The  muscles  show  no  characteristic  change,  but  there  may 
be  rupture  of  some  of  the  fibres  and  small  haemorrhages 
into  the  tissues  due  to  the  excessive  strain  thrown  upon 
them. 


9.  Acute  Poliomyelitis  and  Polio-encephalitis. 

Acute  poliomyelitis  must  now  be  regarded  as  one  of  the  acute 
specific  fevers,  the  specific  lesion  being  an  acute  inflammation 
of  the  central  nervous  system  affecting  the  spinal  cord  more 
frequently  and  more  severely  than  the  brain.  Although  the 
disease  is  sometimes  endemic  and  sometimes  epidemic,  these 
two  forms  show  no  difference  from  one  another  in  regard  to 
their  pathology. 

Aetiology. — Within  recent  years  it  has  been  shown  that  a 
filterable  virus  is  responsible  for  the  disease,  and  that  it  can 
be  obtained  from  the  spinal  cord  of  acute  cases.  Monkeys 
inoculated  with  the  virus  become  paralysed  after  an  interval 
of  a  few  days  and  present  pathological  lesions  identical  with 
those  found  in  the  human  cases.  The  disease  has  also  been 
transmitted  from  one  animal  to  another  by  the  inoculation  of 
spinal  cord  emulsions.  The  virus  can  be  obtained  from  the 
naso-pharyngeal  mucosa  and  intestinal  excreta  of  infected 
animals,  and  there  is  some  reason  to  believe  that  these  sources 
are  responsible  for  the  undoubted  contagiousness  of  the  disease. 
The  virus  is  destroyed  by  half  an  hour's  exposure  to  a  tempera- 
ture of  55°  Centigrade,  but  survives  exposure  to  temperatures 
below  freezing-point.  Certain  animals  can  be  immunised  by 
inoculation  with  the  virus,  and  the  serum  of  such  animals  as 
well  as  the  serum  of  human  beings  who  have  survived  an  attack 
of  the  disease  is  capable  of  modifying  or  neutralising  the  active 
properties  of  the  virus.  Under  normal  conditions  the  incuba- 
tion period  is  not  more  constant  than  that  of  most  specific 
fevers,  and  probably  varies  between  three  and  eight  days.  There 
is  no  doubt  from  clinical  evidence  that  the  disease  can  be 
conveyed  from  one  person  to  another,  even  by  persons  who  are 
not  themselves  subjects  of  an  attack.  In  connection  with 
this  it  is  important  to  note  that  while  the  virus  may  live  in 
an  active  state  for  many  weeks  and  perhaps  months  in  the 

13 


194  INFECTIVE  DISEASES 

nasal  mucosa,  its  life  in  the  spinal  tissues  does  not  appear  to 
be  prolonged  beyond  a  few  days,  and  it  disappears  from  the 
spinal  fluid  before  symptoms  of  paralysis  appear. 

Morphological  and  cultural  characteristics. — The  organism 
has  now  been  grown  on  artificial  culture  media.  For  this 
purpose  pieces  of  sterile  fresh  monkey's  brain  yield  the  highest 
proportion  of  successes,  but  cultures  have  also  been  obtained 
from  filtered  and  glycerinated  tissues.  The  method  employed 
is  similar  to  that  used  by  Noguchi  for  cultivation  of  the 
Spirochaeta  pallida.  Pieces  of  infected  brain  are  put  into  tubes 
of  ascitic  fluid  along  with  a  small  piece  of  fresh  rabbit  kidney, 
and  the  fluid  covered  with  a  layer  of  sterile  paraflin  oil  to 
exclude  air.  Growth  takes  place  in  from  five  to  seven  days, 
occurring  first  in  the  brain  tissue,  and  diffusing  later  through 
the  fluid,  causing  a  slight  turbidity  or  opalescence.  The 
organism  stains  with  the  Giemsa  stain,  appearing  as  minute 
purplish  globoid  bodies  in  clusters  or  short  chains,  and  varying 
from  oa5  jbt  to  0*3  ju  in  size.  It  behaves  variously  with 
Gram's  stain.  Smears  and  sections  of  infected  brain  show 
the  organism  readily,  and  it  has  once  been  found  in  the  heart's 
blood  of  an  infected  monkey. 

Morbid  anatomy. — The  morbid  changes  which  are  present  in 
the  acute  stage  of  this  disease  differ  entirely  from  those  found 
months  or  years  after  the  onset  of  symptoms.  The  former 
illustrate  the  nature  of  the  inflammatory  process;  the  latter 
represent  merely  the  resulting  scars. 

I.  Acute  stage. — The  nature  of  the  acute  changes  is  the 
same  in  all  cases,  whether  they  occur  in  epidemics  or 
sporadically,  and  whether  the  patients  are  children  or  adults, 
but  their  extent  and  intensity  may  vary  considerably.  It 
is  an  invariable  rule  to  find  that  the  extent  of  the  disease 
as  shown  by  a  post-mortem  examination  of  the  tissues  is 
considerably  greater  than  could  be  inferred  from  the  clinical 
symptoms. 

To  the  naked  eye  the  changes  in  the  central  nervous  system 
are  not  very  striking.  The  meninges  are  often  hyperaemic, 
but  present  no  obvious  exudation,  although,  as  will  be  seen 
later,  they  are  sometimes  the  seat  of  a  considerable  cellular 
infiltration.  The  substance  of  the  cord  and  brain,  and 
particularly  the  grey  matter,  appears  hyperaemic  and  oedema- 


ACUTE  POLIOMYELITIS 


195 


Acute  poliomyelitis,  a.  Section  from  high  thoracic  region  stained  by  haema- 
toxyUn  and  van  Gieson  to  show  the  cellular  infiltration  of  the  perivascular 
spaces  and  of  the  grey  matter,  b,  A  higher  power  photograph  of  one  side  of 
the  same  section. 


196  INFECTIVE  DISEASES 

tous      In  some  cases  haemorrhagic  and  necrotic  areas  may  be 
recognised. 

A  section  of  the  spinal  cord  simply  stained  with  haematoxylin 
and  eosin  and  examined  under  a  low  power  presents  features 
which  are  practically  characteristic.  The  grey  matter  is 
darkly  stained  and  stands  out  unusually  well  from  the  white 
columns,  and  the  blood  vessels  both  in  the  white  and  grey 
matter  are  conspicuously  prominent  owing  to  the  fact  that 
their  adventitial  sheaths  are  filled  with  cells  containing  darkly 
stained  nuclei.     A  glance  at  such  a  section  is  instructive  because 


'^  *^ 


t 


Fig.  55. 


Acute  poliomyelitis.     Photograph  showing  the  meningeal  and  perivascular 
cellular  infiltration  in  the  ventral  fissure. 

it  shows  at  once  that  the  process  is  really  a  general  one,  and 
that  it  is  only  the  great  vascularity  of  the  grey  matter  as 
compared  with  the  white,  and  especially  that  of  the  ventral 
horns,  which  suggests  at  first  sight  an  inflammation  limited 
to  a  particular  region. 

The  microscopic  appearances  may  be  described  under  the 
following  heads : 

{a)  Meninges. — The  vessels  of  the  soft  meninges  are  full  of 
blood,  and  their  adventitial  sheaths  often  contain  an  excess  of 
cells  chiefly  of  the  small  round  type,  with  a  variable  proportion 


ACUTE  POLIOMYELITIS 


197 


of  polymorphonuclear  leucocytes.  Similar  cells  are  seen 
scattered  about  in  the  meshes  of  the  arachnoid,  especially  in 
the  neighbourhood  of  the  vessels.  Sometimes  this  meningeal 
infiltration  is  only  found  in  the  lower  parts  of  the  cord ;  in  other 
cases  it  has  been  observed  in  the  higher  parts,  and  even  in  the 
basal  and  vertical  meninges  of  the  brain.     It  shows  up  more 


Fig.  56. 

A  cute  poliomyelitis.     Ventral  horn  cell  preserving  a  fairly  healthy  appear- 
ance and  surrounded  by  intense  small-celled  infiltration. 

prominently  on  the  ventral  than  on  the  dorsal  aspect  of  the 
cord. 

{b)  Grey  matter. — The  vessels  of  the  grey  matter,  whether 
they  are  derived  from  the  anterior  or  the  posterior  systems, 
and  whether  they  are  small  or  large,  all  present  the  same  cellular 
infiltration  of  their  adventitial  sheaths,  which  has  already  been 
described  in  reference  to  the  meningeal  vessels.  The  cells  lie 
chiefly  in  the  spaces  between  the  media  and  the  adventitia,  and 


igS  INFECTIVE  DISEASES 

also  in  the  meshes  of  the  latter  coat.  They  consist  of  small 
cells  similar  to  those  seen  in  the  meningeal  exudation  along 
with  a  few  plasma  cells.  This  cellular  infiltration  affects 
arteries,  veins  and  capillaries  alike,  and  may  be  traced  in  many 
cases  to  the  smallest  capillary  branches.  The  vessels  themselves 
are  generally  engorged  with  blood  which  may  show  signs  of 
thrombosis.  In  addition  to  the  vessel-changes,  the  grey  matter 
itself  is  the  seat  of  great  cellular  proliferation,  which  gives  it  the 
dark  appearance  in  sections  stained  with  haematoxylin.     The 


Fig.  57. 

Acute  poliomyelitis.     Two  ventral  horn  cells  undergoing  destruction  in 
the  midst  of  serous  and  cellular  exudation. 

cells  taking  part  in  this  proliferation  are  probably  various, 
some  being  of  neuroglial,  some  of  endothelial,  and  some  of  blood 
origin.  The  grey  matter  can  also  be  seen  to  be  oedematous, 
and  sometimes  to  contain  capillary  haemorrhages.  The  ganglion 
cells  of  the  grey  matter,  which  include  the  large  ventral  horn 
cells,  the  cells  of  Clarke's  column,  and  those  of  the  dorsal 
horn,  are  found  to  suffer  to  a  greater  or  less  extent.  Owing  to 
the  richer  blood  supply  of  the  ventral  horn,  the  cells  of  that 
region  are  generally  most  affected;  but  definite  changes  are 


ACUTE  POLIOMYELITIS 


199 


frequently  observed  in  the  other  parts.  Speaking  generally, 
those  ganglion  cells  undergo  the  greatest  change  which  are 
most  closely  imbedded  in  the  masses  of  inflammatory  cells, 
but  this  rule  has  its  exceptions,  and  occasionally  healthy-looking 
cells  are  met  with  in  areas  of  intense  inflammatory  reaction. 
On  the  other  hand,  it  is  very  unusual  to  meet  with  definite 
changes  in  ganglion  cells  which  are  far  removed  from    the 


Fig.  58. 

Acute  poliomyelitis.     Changes  in  the  cells  of  Clarke's  column 

and  surrounding  cellular  infiltration. 

inflammatory  centres.  Evidence  of  neuronophagia  is  provided 
by  the  presence  of  neuroglial  and  other  cells  within  the  peri- 
cellular spaces  or  actually  invading  the  protoplasm  of  the 
ganglion  cells.  All  trace  of  myelinated  fibres  and  cell  processes 
is  apt  to  be  lost  in  the  inflamed  areas. 

(c)  White  matter. — The  white  columns  differ  from  the  grey 
matter  in  the  fact  that  they  are  not  nearly  so  richly  supplied 
with  blood,  but  it  is  the  rule  to  find  that  all  vessels  passing 


200 


INFECTIVE  DISEASES 


through  them  from  the  periphery  of  the  cord  towards  the 
central  grey  matter  present  the  same  cellular  infiltration  of  their 
adventitial  sheaths  as  is  found  in  other  parts.  On  the  other 
hand,  it  is  rare  to  find  cell  masses  in  the  white  matter  itself, 
although  occasionally  with  suitable  staining  the  neuroglial 
cells  can  be  shown  to  have  increased  in  size  and  to  have  become 
rounded  in  shape,  sometimes  presenting  two  or  more  nuclei. 
The  columns  of  nerve  fibres  suffer  little,  but  a  certain  amount 
of  degeneration  is  occasionally  met  with,  especially  in  those 
parts  which  border  upon  the  ventral  and  dorsal  horns. 


Fig, 


59. 


Acute  poliomyelitis.     Section  of  spinal  cord  showing  softened  area  with 
granular  corpuscles,  perivascular  infiltration  and  haemorrhage. 

2.  Chronic  stage. — When  the  acute  changes  have  passed  away 
their  results  are  seen  in  various  forms.  In  some  parts  resolu- 
tion may  have  taken  place  with  the  loss  of  a  few  ganglion  cells; 
in  other  parts  necrosis  has  led  to  disappearance  of  the  cellular 
elements ;  in  other  cases  the  necrosis  may  have  produced  actual 
fluid-containing  cavities  in  the  central  parts  of  the  cord  which 
are  pathologically  similar  in  origin  to  the  porencephalic 
cavities  found  in  the  brain.  Sections  stained  by  the  Weigert- 
Pal  method  may  show  some  diffuse  degeneration  of  the  white 


ACUTE  POLIOMYELITIS  201 

columns,  particularly  in  the  neighbourhood  of  the  grey  matter. 
Examination  of  the  nerves  and  muscles  connected  with  dis- 
eased parts  of  the  cord  shows  at  this  stage  signs  of  secondary 
degeneration.  The  muscular  change  is  that  of  a  simple 
atrophy.  The  connective  tissue  seems  to  be  proportionately 
increased  with  the  shrinkage  of  the  muscle  fibres,  and  at  later 
periods  a  certain  amount  of  lipomatosis  or  fatty  infiltration 
may  be  observed  in  some  muscles. 

In  the  acute  stage  of  the  disease  the  morbid  process  can 
often  be  traced  into  the  medulla  oblongata,  and  sometimes 
into  still  higher  parts  of  the  central  nervous  system.  The 
changes  are  similar  to  those  described  in  the  cord,  but,  owing  to 
the  fact  that  the  white  and  the  grey  matter  are  not  so  sharply 
defined  above  the  spinal  cord,  the  distribution  of  inflammation 
has  the  appearance  of  being  less  limited  and  more  irregular. 
This  extension  of  inflammatory  changes  into  the  brain  is  not 
infrequently  found  in  cases  in  which  the  clinical  symptoms 
have  not  suggested  their  presence.  On  the  other  hand,  there 
are  numerous  instances,  especially  in  epidemics  of  the  disease, 
in  which  the  inflammatory  process  is  confined  to  the  brain. 
The  hemispheres,  the  brain-stem,  or  even  the  cerebellum 
may  be  the  chief  site  of  the  morbid  changes. 

It  has  not  yet  been  decided  whether  the  spinal  inflammation 
is  the  result  of  an  infection  through  the  blood  vessels  or  through 
the  lymphatics,  and  opinions  are  more  or  less  divided  on  this 
point.  But  however  the  infection  reaches  the  cord,  there  seems 
little  doubt  that  the  inflammation  spreads  in  it  by  the  lym- 
phatics, as  it  always  shows  a  gradual  diminution  on  passing  from 
the  level  of  greatest  involvement  to  levels  that  are  not  at  all 
affected.  The  spread  in  the  cord  seems  to  be  mainly  upwards 
and  downwards.  Thus  one  ventral  horn  may  be  apparently 
intact,  although  the  other  is  completely  destroyed  over  several 
segments.  Similarly,  it  is  not  uncommon  to  find  very  extensive 
paralysis  of  one  upper  or  lower  limb,  with  little  or  no  paralysis 
of  its  fellow.  In  such  cases,  however,  the  history  usually 
suggests  that  both  ventral  horns  have  been  attacked  in  the 
first  instance,  but  whereas  one  has  recovered  rapidly  and 
completely,  the  other  has  undergone  much  more  severe  injury. 
That  the  cellular  infiltration  of  the  meninges  which  is  found  in 
fatal  cases  is  also  present  in  non-fatal  cases  is  proved  by  the 


202  INFECTIVE  DISEASES 

fact  that  lumbar  puncture  usually  demonstrates  a  lympho- 
cytosis of  the  cerebro-spinal  fluid. 

The  relation  of  the  anatomical  to  the  clinical  phenomena. — A 
consideration  of  the  pathological  process  just  described  explains 
the  clinical  features  of  this  disease.  In  the  first  place,  it  is 
clear  that  the  virus  has  no  specific  action  upon  the  nerve  cells, 
and  that  the  latter  suffer  irregularly  from  the  inflammatory 
exudation  in  which  they  become  submerged.  In  some  regions 
the  ventral  cornual  cells  disappear  rapidly,  and  these  regions 
correspond  to  the  muscular  territories  in  which  atrophy  is 
rapid,  complete  and  permanent.  In  other  spinal  segments  the 
ventral  horn  cells  undergo  a  process  of  partial  degeneration 
with  chromatolysis  and  displacement  of  their  nuclei,  and  these 
areas  find  their  clinical  counterpart  in  the  muscles  which  under- 
go atrophy,  but  which,  after  a  considerable  interval  of  time, 
regenerate  either  completely  or  in  part.  Finally,  there  are 
the  cells  which  retain  a  more  or  less  healthy-looking  appearance 
in  spite  of  surrounding  inflammation.  Such  cells  may,  and 
doubtless  often  do,  suffer  from  some  temporary  functional 
disturbance,  and  they  are  represented  clinically  by  those 
muscles  which  are  paralysed  for  a  few  hours  or  a  few  days  only, 
and  which  rapidly  recover  their  normal  activity.  Evidence 
of  the  occasional  involvement  of  the  white  matter  is  afforded 
clinically  by  the  presence  of  reflex  changes,  increased  knee 
jerks,  ankle  clonus  and  extensor  responses,  in  a  small 
minority  of  cases. 

10.  Lethargic  Encephalitis. 

Definition. — This  is  a  rather  rare  disease  which  may  occur 
in  epidemic  form.  It  is  characterised  by  a  tendency  to  somno- 
lence and  slight  delirium  from  which  the  patient  is  easily  roused, 
and  by  various  nervous  manifestations  of  which  the  commonest 
is  paralysis  of  the  cranial  nerve  nuclei,  especially  the  oculo- 
motor. It  may,  however,  affect  chiefly  the  cerebral  hemi- 
spheres or  the  basal  ganglia.  When  it  occurs  in  epidemic  form 
the  cases  are  comparatively  few  in  number,  and  are  scattered 
irregularly  through  a  district.  There  is  seldom  any  evidence  of 
direct  infection,  although  in  a  few  instances  two  members  of  a 
family  have  been  affected  at  an  interval  of  a  few  days  to  a 
fortnight. 


LETHARGIC  ENCEPHALITIS  203 

Aetiology. — Many  observers  with  long  experience  in  the 
transmission  of  poUomyehtis  have  failed  to  transmit  the  virus 
of  lethargic  encephalitis,  but  recently  Mcintosh  appears  to 
have  been  successful  in  infecting  monkeys  and  passing  the 
disease  from  them  to  rabbits.  He  states  that  it  always  breeds 
true,  constantly  producing  cerebral  symptoms  which  may 
progress  through  many  days,  whereas  poliomyelitis  usually 
affects  the  limbs  of  infected  animals.  Lethargic  encephalitis 
seems,  therefore,  to  be  of  different  aetiology  from  poliomyelitis 
and  polio-encephalitis.  It  differs  from  this  disease  also  in 
seasonal  incidence,  occurring  mostly  in  the  winter  and  spring 
months,  whereas  poliomyelitis  is  more  common  in  the  summer 
and  autumn  months.  Its  clinical  history  is  also  different,  as 
many  cases  go  on  for  weeks  with  periodic  exacerbations  of 
nervous  symptoms.  It  affects  all  ages  indifferently,  and 
affects  children  less  commonly  than  adults. 

Clinical  pathology. — The  fluid  obtained  by  lumbar  puncture 
varies  in  different  cases.  In  about  50  per  cent,  of  cases  it  shows 
no  abnormality,  either  as  regards  cells  or  albumen.  In  other 
cases  a  diffuse  blood  admixture,  with  a  corresponding  albumen 
increase,  and  slight  lymphocytosis  indicates  subarachnoid 
haemorrhage.  In  still  others  a  cell  increase  is  present,  with 
or  without  a  noticeable  increase  in  albumen.  The  cells  are 
entirely  of  a  mononuclear  type,  many  large  forms  being 
present  in  addition  to  the  small  lymphocyte.  In  no  cases 
which  we  have  examined  has  there  been  the  fibrin  coagulum 
which  is  so  commonly  found  in  poliomyelitis,  nor  have  poly- 
morphonuclear cells  been  present. 

Morbid  anatomy. — The  macroscopic  appearances  during  the 
early  stages  are  often  striking  and  almost  pathognomonic, 
the  surface  of  the  brain  being  tinged  a  deep  cherry  red,  and 
showing  numerous  small  subarachnoid  haemorrhages.  On 
section  the  grey  matter  everywhere  is  of  a  purplish  red  colour, 
and  the  larger  blood  vessels  stand  out  prominently.  Smaller 
or  larger  areas  of  haemorrhage  into  the  grey  or  white  matter 
may  be  seen  either  in  the  cerebrum,  or  more  commonly,  in 
the  mid-brain  and  pons.  In  some  cases  there  is  evidence  of 
thrombosis  of  some  of  the  larger  cortical  veins  or  arteries,  and, 
in  connection  with  the  latter,  areas  of  infarction  of  the  brain 
substance  may  be  seen.     Where  the  brain-stem  is  more  affected 


204 


INFECTIVE*  DISEASES 


Fig.  6o. 

Lethargic  encephalitis .  A  vessel  is  seen  with  a  fibrinous  clot  in  its  lumen, 
and  surrounded  by  a  thick  ring  of  small  round  cells.  Great  glial  overgrowth 
is  seen  in  the  surrounding  nervous  tissue. 


r^.  t 


-v.: 


'^^\   5ri.'3 


^' 


#--*'*A.,^v-"L.>-»r.-7.::.;.  ■■ 


Fig.  6i. 
Lethargic   encephalitis.     Cortex.     The   typical    "  cuffing  "    of   the   medium 
and  small-sized  veins  of  the  cortex  is  shown,  as  well  as  the  great  congestion 
of  the  capillaries. 


LETHARGIC  ENCEPHALITIS  205 

than  the  fore-brain,  the  only  obvious  appearance  may  be  a 
basal  haemorrhage  in  the  region  of  the  oculomotor  sulcus, 
spreading  thence  over  the  cerebellum  and  pons.  It  is  usual 
to  find  that  the  grey  matter  of  the  cord,  at  any  rate  in  the 
cervical  region,  also  shows  some  hyperaemia. 

Microscopically,  in  the  early  stages  the  chief  changes  are  the 
great  congestion  of  all  the  blood  vessels,  even  of  the  smallest 
capillaries,  and  a  diffuse  alteration  in  the  nerve  cells,  most  of 


Fig.  62. 

Lethargic  encephalitis.  View  of  longitudinal  section  of  a  small  blood 
vessel  in  the  cortex.  The  adventitial  sheath  is  seen  to  contain  numerous 
small  round  cells.     Two  petechial  haemorrhages  are  seen  close  to  the  vessel. 

which  show  a  smaller  or  greater  degree  of  chromatolysis  and 
increase  of  pigment.  While  some  nerve  cells  in  any  section 
are  more  affected  than  others,  it  is  usual  at  this  stage  to  find 
some  change  in  all.  The  more  affected  cells  are  often  ringed 
with  three  or  four  round  cells,  which  appear  to  be  chiefly  of 
vascular  origin,  and  similar  small  round  cells  can  be  traced 
emerging  from  the  walls  of  the  capillaries  and  permeating  the 
brain  tissue.  It  is,  however,  the  exception  to  find  such  clumps 
of  round  cells  as  are  found  in  the  grey  matter  of  the  cord  in 


206 


INFECTIVE  DISEASES 


Fig.  63. 
Lethargic  encephalitis.     Cortex.     A  capillary  vessel  is  seen  in  the  centre  of 
the  field,  showing  short  chains  of  small  round  cells  along  its  walls. 


Fig.  64. 

Lethargic  encephalitis.     View  of  cortex  and  meninges  to  show  the  patchy 
infiltration  of  the  meninges  with  small  cells. 


LETHARGIC  ENCEPHALITIS  207 

poliomyelitis,  and  polymorphonuclear  cells  are  practically  never 
found  outside  the  vessels. 

Another  striking  appearance,  athough  by  no  means  a 
constant  one,  is  the  infiltration  of  the  Virchow-Robin  space 
with  small  round  cells,  among  which  a  small  proportion  of 
plasma  cells  may  be  found.  This  appears  to  occur  at  a  slightly 
later  stage  of  the  disease  than  the  changes  previously  mentioned. 
The  greatest  degree  of  infiltration  is  seen  in  the  walls  of  the 
venules,  and  in  some  cases  can  be  traced  along  them  into  the 
subarachnoid  space,  where  it  is  not  uncommon  to  find  collections 
of  round  cells  close  to  the  medium-sized  veins.  Small  haemor- 
rhages are  often  seen  distending  the  so-called  perivascular  space 
of  His,  and  tearing  away  and  pressing  back  the  neuroglia  from 
the  vessel  wall.  Smaller  or  larger  haemorrhages  into  the 
tissues  may  also  occur.  Thrombosis  of  venules  and  even  of 
arterioles  is  not  uncommon,  and  the  majority  of  the  vessels 
in  a  section  may  be  so  affected,  but  as  a  rule  it  is  patchy  in 
distribution  and  only  affects  one  or  two  venules  in  each 
section. 

At  a  later  stage  there  may  be  evidence  of  softening  of  small 
areas  in  the  brain-stem  or  cerebrum.  The  perivascular  infiltra- 
tion is  usually  more  pronounced.  A  large  proportion  of  the 
nerve  cells  have  returned  to  their  normal  appearance,  but  those 
more  severely  damaged  by  the  disease  are  being  attacked  by 
neuronophages,  and  are  in  all  stages  of  dissolution. 

Correlation  of  anatomical  and  clinical  phenomena. — The 
general  lethargic  or  somnolent  condition  of  the  patient  may 
be  partly  accounted  for  by  the  general  intoxication,  but  its 
striking  remissions  suggest  that  it  may  be  due  to  some 
degree  of  hydrocephalus  resulting  from  intermittent  blocking 
of  the  aqueduct  of  Sylvius.  The  more  sudden  nervous 
manifestations,  such  as  ocular  palsies,  facial  palsy  or 
hemiplegia,  appear  to  be  due  to  thrombosis  of  the  vessels 
supplying  the  affected  area  or  to  haemorrhagic  destruction 
of  this  part  of  the  brain.  Many  of  the  more  intractable 
sequelae  are  also  probably  due  to  vascular  changes,  but  some, 
such  as  tremors  and  athetoid  or  choreiform  movements,  may 
be  due  to  an  extensive  destruction  of  the  nerve  cells  of  the 
cortex  or  the  basal  ganglia. 


208 


INFECTIVE  DISEASES 


i 


\ 


A.*1 


Fig.  65. 

Lethargic  encephalitis.     Blood  vessel  in  medulla  filled  with  fibrinous  clot, 

which  is  being  absorbed  by  phagocytic  mononuclear  cells. 


Fig.  66. 

Lethargic  encephalitis.  Medium-sized  artery  on  the  cortex  partially 
obstructed  with  haemorrhage  in  its  walls,  and  leading  to  small  wedge-shaped 
area  of  infarction,  a  corner  of  which  is  seen  in  the  right  lower  corner  of  the 
figure. 


LANDRY'S  PARALYSIS  209 

II.  Landry's  Paralysis. 

The  term  Landry's  paralysis  has  been  used  by  different 
observers  to  describe  a  number  of  different  pathological 
conditions,  although  in  the  first  place  it  was  applied  to  a 
rapidly  fatal  disease  of  which  the  pathology  and  morbid 
anatomy  were  quite  unknown.  Some  of  the  cases  which  have 
gone  by  this  name  have  been  instances  of  multiple  neuritis, 
others  of  acute  poliomyelitis.  For  the  present  purpose  the 
term  Landry's  paralysis  will  be  applied  to  a  morbid  condition 
which  corresponds  closely  in  its  clinical  features  with  the  cases 
described  by  Landry,  and  which  displays  anatomical  changes  of 
so  slight  a  character  that  they  would  not  have  been  recognisable 
by  the  methods  employed  fifty  years  ago.  Using  the  name  in 
this  sense  we  know  practically  nothing  about  the  aetiology  of 
the  disease  beyond  the  fact  that  it  attacks,  as  a  rule,  healthy 
adults,  chiefly  males  between  twenty  and  forty  years  of  age. 
In  some  instances  the  patients  have  suffered  previously  from 
some  infective  disorder  such  as  gonorrhoea,  influenza,  or 
typhoid  fever,  and  in  other  instances  their  work  has  exposed 
them  to  extreme  variations  of  temperature,  but  there  is  no 
evidence  sufficiently  strong  to  regard  these  historical  facts  as 
really  important  from  an  aetiological  point  of  view.  The  same 
obscurity  may  be  said  to  involve  the  question  of  bacteriology, 
and  it  is  not  possible  to  say  definitely  whether  the  disease  has 
a  specific  cause  or  whether  it  may  result  from  exposure  to 
various  poisons  of  bacterial  or  other  origin.  Many  cases  have 
been  examined  from  a  bacteriological  point  of  view  with 
negative  results.  On  the  other  hand,  a  few  have  provided 
discoveries  of  some  interest.  In  one  instance  a  diplococcus 
resembling  the  pneumococcus  was  cultivated  from  the  patient's 
blood,  and  this  organism  gave  rise  to  symptoms  of  paraplegia 
when  injected  into  a  rabbit.  In  another  case  an  organism 
was  isolated  from  the  blood  of  the  patient  and  also  seen  under 
the  microscope  in  the  loose  vascular  tissue  forming  the  external 
layer  of  the  spinal  theca  after  the  patient's  death.  A  subdural 
injection  of  this  organism  into  a  rabbit  produced  after  some 
days  a  rapidly  spreading  paralysis,  and  the  same  coccus  was 
discovered  in  the  theca  of  the  rabbit  and  isolated  from  its  blood. 
A  somewhat  similar  microbe  has  been  found  in  the  blood  and 

14 


210  INFECTIVE  DISEASES 

cerebro-spinal  fluid  of  a  non-fatal  case,  but  in  that  instance  no 
results  were  obtained  from  experimental  inoculation. 

Pathogenesis. — There  are  not  sufficient  data  for  constructing 
a  definite  theory  for  the  origin  of  this  disease,  and  we  must  be 
content  for  the  present  to  assume  that  it  results  from  some  form 
of  infection,  although  we  are  not  fully  acquainted  with  the 
nature  of  the  responsible  virus  nor  of  its  mode  or  path  of 
entry.  For  some  reasons  it  seems  likely  that  the  bacteria  do 
not  themselves  infest  the  spinal  cord,  but  exert  their  toxic 
influence  upon  that  organ  from  a  distance,  possibly  through  the 
medium  of  the  cerebro-spinal  and  lymphatic  fluids. 

Morbid  anatomy. — To  the  naked  eye  the  central  and  peri- 
pheral nervous  systems  present  nothing  remarkable,  with  the 
exception  of  some  general  hyperaemia  of  the  cord.  The  latter, 
however,  has  a  firm  consistence  before  it  is  cut,  provided  that 
post-mortem  decomposition  has  not  commenced.  After  section 
the  vascularity  of  the  grey  matter  may  be  noticeable,  and  may 
stand  out  somewhat  conspicuously  from  the  white  columns. 
It  is  sometimes  even  possible  to  detect  small  haemorrhages  in 
the  ventral  horns.  There  is  no  exudation  on  the  surface.  The 
degree  of  microscopic  change  varies  to  some  extent  with  the 
length  of  the  clinical  symptoms,  and  in  some  rapidly  fatal  cases 
it  may  be  impossible  to  detect  any  definite  abnormalities.  In 
the  majority  of  cases,  however,  a  careful  examination  of  the 
spinal  cord  by  means  of  the  Nissl  and  Marchi  methods  discovers 
the  following  changes. 

1.  Cells. — A  certain  number  of  the  ganglion  cells,  especially 
those  of  the  ventral  horns  and  of  Clarke's  column,  present  either 
early  pericentral  chromatolysis  or  a  more  complete  loss  of  the 
chromatin  granules,  together  with  some  displacement  of  the 
nucleus.  The  more  marked  changes  are  usually  found  in 
the  lumbo-sacral  enlargement,  and  this  is  not  surprising  when 
it  is  remembered  that  the  lower  limbs  are  usually  the  first  to 
be  paralysed. 

2.  Myelin. — The  medullary  sheaths  of  the  spinal  cord  nerve 
fibres,  and  to  a  less  extent  those  of  the  peripheral  nerve  fibres, 
may  show  some  diffuse  fatty  change  quite  unlike  that  of 
secondary  degenerations.  In  longitudinal  sections  small 
droplets  of  altered  myelin  are  seen  lying  singly  or  two  or  three 
together  within  or  between  the  fibres,  but  not  filling  the  whole 


LANDRY'S  PARALYSIS  211 

area  of  the  medullary  sheaths.  This  appearance  may  be  found 
in  many  toxic  states  unassociated  with  definite  paralysis,  and 
does  not  therefore  necessarily  indicate  a  loss  of  function  on  the 
part  of  the  nerve  fibres. 

Neuroglia  and  blood  vessels. — There  is  no  evidence  of  neuro- 
glial proliferation,  although  some  of  the  cells  may  appear 
to  be  slightly  swollen.  The  blood  vessels  are  somewhat 
engorged,  but  otherwise  healthy  in  appearance.     Very  rarely  a 


Fig.  67. 

Landry's  paralysis.     One  ventral  horn  cell  shows  chromatolysis  with 
displacement  of  nucleus. 

slight  excess  of  small  round  cells  may  be  seen  in  the  immediate 
neighbourhood  of  one  or  two  vessels,  but  the  paucity  of  any 
such  cellular  infiltration  is  in  striking  contrast  to  the  anatomical 
changes  seen  in  acute  poliomyelitis.  The  above  are  the  only 
morbid  changes  found  in  the  majority  of  cases  at  the  time  of 
death.  Occasionally,  when  the  fatal  termination  has  been 
postponed  for  a  longer  period,  the  Marchi  method  will  reveal 
the  presence  of  true  Wallerian  degeneration  which  may   be 


212  INFECTIVE  DISEASES 

secondary  to  the  cell  changes.  If  this  exists,  some  atrophy 
may  also  be  present  in  some  of  the  skeletal  muscles.  No 
constant  changes  have  been  found  in  other  organs,  although  an 
enlarged  spleen  and  enlarged  mesenteric  glands  are  by  no  means 
uncommon. 

12.  Herpes  Zoster. 

Aetiology. — Herpes  zoster  is  included  in  this  chapter  as,  for 
various  reasons,  there  seems  little  doubt  that  it  is  caused  by 
a  micro-organism  of  either  bacterial  or  protozoal  nature.  The 
pathology  is  characterised  by  acute  inflammation  of  a  dorsal 
root  ganglion;  and  although  there  is  practically  no  difference 
between  the  histological  appearances  of  this  disease  and  those 
of  epidemic  poliomyelitis,  allowance  being  made  for  the  part 
of  the  nervous  system  attacked,  there  is  no  evidence  that  the 
same  organism  is  responsible  for  both.  The  observed  facts 
seem,  indeed,  to  point  in  the  opposite  direction,  as  we  do  not 
see  an  increased  number  of  cases  of  herpes  during  an  epidemic 
of  poliomyelitis,  nor  do  analogous  lesions  occur  in  the  ex- 
perimental transmission  of  the  virus  of  poliomyelitis.  On  the 
other  hand,  the  similarity  between  the  two  diseases  is  incon- 
testable. Both  are  characterised  by  an  acute  inflammation  of 
the  nervous  system  with  special  incidence  on  one  locality,  by 
the  presence  of  a  great  degree  of  small-celled  infiltration  and 
vascular  congestion  with  haemorrhages  at  the  site  of  the  lesion, 
and  by  lymphocytosis  of  moderate  degree  in  the  cerebro-spinal 
fluid.  The  general  febrile  symptoms  are  not  dissimilar,  and 
both  diseases  occur  either  as  sporadic  cases  or  in  epidemics 
of  less  or  greater  extent,  in  which  there  is  no  direct  transmission 
of  infection,  and  both  protect  the  patients  from  subsequent 
attacks.  The  immunity  in  herpes  is  not,  however,  so  absolute 
as  in  poliomyelitis,  as  Head  and  Campbell  in  400  cases  found 
four  instances  of  a  second  attack. 

Herpes  zoster  may  occur  at  any  period  of  life,  although  it 
tends  to  be  more  severe  as  age  advances.  It  occurs  in  the 
course  of  degenerative  diseases  of  the  central  nervous  system, 
such  a;s  tabes,  general  paresis,  and  disseminated  sclerosis; 
and  in  some  of  these  may  be  symptomatic.  But  its  course 
and  pathology  in  such  cases,  and  the  rarity  of  its  occurrence, 
suggest  that  here,  too,  we  are  dealing  with  true  idiopathic  herpes 


HERPES  ZOSTER  213 

zoster.  On  the  other  hand,  a  rash  similar  in  appearance  and 
distribution  may  occur  in  the  course  of  destructive  lesions  of 
the  cord  and  its  envelopes  which  affect  the  dorsal  root  ganglia. 
This  may  be  seen  in  the  course  of  Pott's  disease  or  cancer  of  the 
vertebrae,  or  after  severe  traumatism  affecting  the  spine. 
These  cases  are  probably  due  to  a  lesion  of  the  ganglion  either 
directly  or  by  interference  with  its  blood  supply. 

Herpes  lahialis,  or  facialis,  may  occur  in  the  course  of  acute 
infective  diseases.  Examination  of  the  Gasserian  ganglion 
in  such  cases  has  shown  inflammatory  lesions  probably  due 
to  the  attacking  organism.  There  is  thus  some  pathological 
relationship  between  the  two  varieties  of  herpes. 

Macroscopic  appearances. — In  the  early  stages  the  affected 
ganglion  is  swollen  and  hyperaemic.  On  section  it  may  have  a 
uniform  pinkish  tint,  or  there  may  be  haemorrhages  visible  to 
the  naked  eye.  The  nerve  in  relation  to  it  may  also  be 
swollen. 

Microscopically  the  chief  changes  seen  in  the  ganglion  are 
congestion  of  all  the  vessels,  numerous  small  haemorrhages 
around  them,  and  infiltration  of  the  tissues  with  small  round 
cells.  These  seem  to  be  more  numerous  in  relation  to  some 
arterioles  than  others,  especially  towards  the  dorsal  side  of  the 
ganglion.  Some  of  the  nerve  cells  are  completely  destroyed, 
others  show  various  degrees  of  degeneration,  being  swollen 
and  staining  diffusely,  but  chromolytic  changes  are  not  seen. 
Many  of  them  are  surrounded  by  round  cells  which  have  invaded 
their  capsule,  and  seem  to  be  acting  as  phagocytes  by  a  process 
of  neuronophagy.  Others  escape  completely  and  show  no  altera- 
tion in  their  Nissl  granules.  The  sheath  of  the  ganglion  is 
infiltrated  with  round  cells  and  its  vessels  engorged,  and  there 
may  be  some  oedema  between  its  layers.  Similar  changes  are 
seen  in  the  nerve  close  to  its  emergence  from  the  ganglion. 

After  eleven  days  degeneration  is  found  by  Marchi's  method 
both  in  the  dorsal  nerve  roots  and  in  the  peripheral  nerves.  It 
has  been  traced  into  the  cord  and  up  the  dorsal  columns 
for  a  varying  distance,  and  also  down  the  peripheral  nerves 
as  far  as  the  terminal  twigs  to  the  skin.  It  is  similar  in 
character  to  Wallerian  degeneration.  At  a  later  stage  the 
changes  seen  in  the  ganglia  and  peripheral  nerves  are  of  a 
cicatricial  nature,  and  may  not  be  obvious  unless  the  original 


214  INFECTIVE  DISEASES 

inflammation  has  been  severe  and  fairly  extensive,  but  some 
degree  of  sclerosis  can  usually  be  found  both  in  the  ganglion 
and  its  capsule  and  in  the  peripheral  nerves. 

Head  and  Campbell  in  392  cases  found  that  certain  ganglia 
were  more  often  affected  than  others ;  thus,  those  on  the  dorsal 
roots  from  the  fifth  cervical  to  the  second  thoracic  and  from 
the  third  lumbar  downwards  were  particularly  exempt — that  is, 
those  in  the  areas  corresponding  to  the  nerve  supply  of  the 
limbs.  The  Gasserian  ganglion  is  frequently  affected,  and  the 
changes  in  it  are  similar  to  those  in  the  spinal  root  ganglia. 

13.  Chorea. 

Aetiology. — This  disease  is  common  in  childhood  and 
adolescence,  and  rare  after  twenty  years  of  age.  It  has  no 
direct  hereditary  basis,  but  more  than  one  member  of  a  family 
of  the  same  generation  is  often  affected.  Nervous,  excitable 
children,  very  often  those  who  are  intellectually  well  equipped, 
appear  to  be  specially  disposed  to  the  disease,  and  girls  are 
more  frequently  affected  than  boys.  Climatic  influences  are 
not  marked,  but  there  are  certainly  seasonal  variations  in  the 
prevalence  of  the  disease. 

The  most  important  aetiological  factor  is  the  relationship  of 
chorea  to  acute  rheumatism,  and  many  authorities  regard  chorea, 
rheumatic  arthritis,  rheumatic  endocarditis,  and  pericarditis  as 
manifestations  of  the  same  virus  affecting  different  tissues. 
On  this  theory  there  is  no  difficulty  in  understanding  why 
arthritis  precedes  chorea  in  the  majority  of  instances,  and 
why  less  commonly  chorea  may  appear  before  attention 
has  been  drawn  to  the  rheumatic  poison  by  the  occurrence  of 
joint  trouble.  The  frequent  association  of  chorea  with  endo- 
carditis and  myocarditis  is  further  evidence  of  the  affinity 
between  these  various  manifestations  of  some  specific  virus. 
In  recent  years  Poynton  and  Payne  have  succeeded  in  cultivat- 
ing from  the  cerebro-spinal  fluid  of  choreic  patients  a  diplo- 
coccus  identical  with  that  which  they  have  described  as  the 
Diphcoccus  rheiimaticiis,  and  they  have  also  produced  move- 
ments in  rabbits  which  bear  a  resemblance  to  the  movements  in 
human  chorea.  The  diplococcus  has  also  been  found  in  the  pia 
mater  and  cerebral  tissues,  and  has  been  isolated  from  the 
blood  of  patients  suffering  from  chorea. 


CHOREA  215 

Pregnancy  appears  to  have  a  special  influence  in  evoking  an 
attack  of  chorea,  most  commonly  in  the  case  of  women  who 
have  had  previous  attacks  or  who  give  a  history  of  the 
rheumatic  diathesis. 

The  relationship  of  emotion,  and  particularly  of  fright,  with 
the  onset  of  symptoms  has  often  been  remarked,  but  the 
observation  of  parents  with  regard  to  such  coincidences  is  not 
very  often  entirely  trustworthy.  It  would  not,  however, 
be  very  surprising  if  fright  were  responsible  for  exag- 
gerating slight  symptoms  of  chorea  which  may  have  been 
overlooked,  or  even  for  evoking  them  in  a  predisposed 
subject. 

Pathogenesis. — The  accumulation  of  evidence  supports  the 
view  that  chorea  is  an  infective  disease  of  microbic  origin, 
although  there  may  be  room  for  doubt  with  regard  to  the 
specificity  of  the  virus.  The  old  belief  that  numerous  emboli 
of  the  cerebral  vessels  were  responsible  for  the  clinical  symptoms 
of  the  disease  has  not  been  supported  by  the  pathological 
examination  of  recent  cases,  and  the  absence  in  many  cases  of 
any  source  of  the  emboli  in  the  shape  of  valvular  vegetations 
further  discredits  this  theory. 

No  agreement  has  been  arrived  at  with  regard  to  the  actual 
site  of  the  morbid  changes  which  are  responsible  for  the  clinical 
manifestations  of  the  disease.  The  dendrites,  the  cortical  cells, 
the  cells  of  the  basal  ganglia  and  of  the  brain-stem  have  all  been 
indicted  by  different  authorities,  and  blame  has  been  attached 
to  those  parts  of  the  nervous  system  which  bring  the  influence 
of  the  cerebellum  to  bear  upon  the  cortico-spinal  and  rubro- 
spinal systems. 

Morbid  anatomy. — Macroscopical  changes  in  the  central 
nervous  system  in  cases  of  chorea  have  usually  been  conspicuous 
by  their  absence,  but  attention  has  been  called  to  the  occasional 
presence  of  hyperaemia  and  of  small  thrombotic  lesions  which, 
however,  are  by  no  means  constant.  The  same  remark  applies 
to  the  occurrence  of  small  perivascular  haemorrhages  and  slight 
neuroglial  proliferations.  According  to  some  authors,  evidences 
of  slight  inflammation  and  small  foci  of  necrosis  with  exudation 
are  more  common  in  the  basal  ganglia  than  elsewhere.  Under 
the  microscope  similar  changes  have  often  been  described,  as 
well   as  chromatolysis  of  ganglion  cells  in  the  cortex  and 


2i6  TRYPANOSOMIASIS 

basal  ganglia.  Micro-organisms  of  various  kinds  have  been 
detected  in  addition  to  the  Diplococcus  rheumaticus  found  by 
Poynton  and  Payne  and  Gordon  Holmes. 

At  the  present  time  it  is  hardly  justifiable  to  do  more  than 
mention  the  various  microscopical  findings  which  have  been 
referred  to,  and  it  is  too  early  to  express  a  decided  opinion  as 
to  the  significance  of  each  or  to  characterise  any  of  them  as 
essential  factors  in  the  morbid  anatomy  of  chorea. 

Relationship  of  anatomical  to  clinical  phenomena. — We  are  not 
in  a  position  to  correlate  the  movements  so  typical  of  chorea 
with  any  particular  lesion  in  any  particular  part  of  the  brain, 
but  there  is  a  general  tendency  to  regard  choreiform  movements 
as  a  manifestation  of  disturbance  in  the  functions  of  the  basal 
gangliaralher  than  in  those  of  the  motor  cortex.  The  asthenia, 
which  may  sometimes  be  very  profound  in  choreic  patients, 
may  be  looked  upon  as  evidence  of  the  influence  exerted  by  an 
infective  virus  upon  the  nerve  cells  of  the  brain,  and  the  oc- 
casional presence  of  reflex  changes,  such  as  an  extensor  plantar 
response,  points  to  the  conclusion  that  the  pyramidal  tracts 
may  at  times  suffer  severely  from  toxic  effects.  Hyperpyrexia 
and  mania  are  occasionally  serious  complications  in  the  course 
of  chorea,  and  are  generally  attributed  to  the  effects  of  poison 
and  exhaustion  on  particular  regions  of  the  central  nervous 
system. 

14.  Trypanosomiasis. 

This  is  a  chronic  infective  disease  affecting  the  nervous  system 
in  the  later  stages,  when  it  produces  the  clinical  condition  called 
"  negro  lethargy  "  or  "  sleeping  sickness."  It  occurs  in 
endemic  and  epidemic  form  in  most  parts  of  Central  Africa, 
and  has  been  found  as  far  south  as  Rhodesia. 

The  infective  agent  is  one  of  two  species  of  trypanosome, 
T.  gambiense  and  T.  rhodesiense,  which  are  transmitted  to  man 
by  the  bites  of  the  tsetse  flies,  Glossina  palpalis  and  G.  morsita'  s 
respectively. 

When  transferred  to  the  human  subject,  the  trypanosomes 
enter  the  blood  stream  and  multiply.  They  never,  however, 
become  very  numerous  in  human  blood,  and  are  not  easily 
found  in  direct  blood  smears.  It  is  better  to  search  for  them 
in  the  centrifugalised  deposit  of  citrated  blood,     They  also 


RABIES  217 

enter  the  lymphatics,  and  are  readily  found  at  any  stage  of  the 
disease  in  the  fluid  from  enlarged  glands.  They  are  rarely 
present  in  the  cerebro-spinal  fluid  in  the  earlier  stages  of  the 
disease,  but  may  be  found  there  in  almost  every  case  after  the 
characteristic  symptoms  of  "  sleeping  sickness  "  have  made 
their  appearance.  They  may  also  be  found  there  during  attacks 
of  pyrexia. 

The  chief  change  in  the  gross  appearance  of  the  brain  and 
spinal  cord  is  a  diffuse  opacity  of  the  pia-arachnoid,  which  may 
be  abnormally  adherent  to  the  cortex  of  the  brain.  There 
may  also  be  a  moderate  degree  of  hydrocephalus.  The 
cerebro-spinal  fluid  is  sometimes  slightly  yellow  in  colour. 

Microscopically  the  characteristic  feature  of  the  disease  is  a 
crowding  of  the  perivascular  lymphatics  and  of  the  meshes  of 
the  pia-arachnoid  by  small  round  cells.  This  affects  different 
parts  of  the  brain  and  cord  in  varying  degree,  but  is  present  to 
some  extent  all  over.  A  similar  condition  is  present  throughout 
the  lymphatic  channels  of  the  body,  and  is  specially  noticeable 
in  the  intestinal  lymphatics.  The  other  changes  in  the  central 
nervous  system  appear  either  to  be  secondary  to  this  (Mott) 
or  due  to  toxins  derived  from  the  parasite.  In  the  cortex 
of  the  brain  the  pyramidal  cells  may  show  loss  of  their  Nissl 
granules,  displacement  of  their  nuclei  or  diffuse  staining  of 
the'r  protoplasm.  There  is  also  a  diminution  of  the  fibres  of 
the  supraradial  and  tangential  layers.  In  the  cord  there  is  a 
diffuse  sclerosis.  In  contrast  to  the  appearances  observed 
in  general  paralysis  of  the  insane,  there  are  no  changes  in 
the  vessels. 


15.  Hydrophobia  or  Rabies. 

Definition. — Rabies  is  an  acute  infective  disease  of  the 
nervous  system  communicated  from  animal  to  animal,  or  from 
animal  to  man  through  the  saliva,  either  by  biting  the  healthy 
skin  or  by  licking  an  abraded  surface.  The  incubation  period 
varies  with  the  size  of  the  infected  animal  and  with  the  distance 
of  the  site  of  inoculation  from  the  central  nervous  system  and 
especially  from  the  brain.  Thus,  in  the  human  subject,  infection 
through  the  skin  of  the  face  or  neck  brings  on  the  disease  after 
a  much  shorter  incubation  period  than  when  the  hands  or  legs 


2i8  INFECTIVE  DISEASES 

are  bitten.  Usually,  in  the  human  subject,  it  varies  from  twenty 
to  fifty  days,  but  cases  have  been  reported  in  which  it  has 
extended  to  two  or  even  five  years.  When  the  disease  is 
established  it  is  uniformly  fatal. 

Causative  organism. — In  1903  Negri  described  certain  minute 
bodies  in  the  nerve  cells  of  the  central  nervous  system  in  dogs 
affected  with  rabies.  When  appropriately  stained  these  appear 
as  small  bodies  of  from  0*5  to  18  //-  in  diameter,  composed 
of  an  oxyphil  cytoplasm,  with  a  basophil  "  central  body  "  and 
basophil  granules,  and  surrounded  by  a  definite  limiting 
membrane. 

In  shape  these  bodies  are  rounded,  oval,  triangular  or 
spindle-shaped.  They  are  found  in  the  substance  or  the  pro- 
cesses of  the  ganglion  cells  of  the  brain,  spinal  cord  and  spinal 
ganglia,  and  in  the  cells  of  Purkinje  in  the  cerebellum.  Some- 
times they  lie  immediately  around  the  cell.  They  are  most 
constantly  found  in  the  large  cells  of  the  cornu  ammonis  in 
dogs.  In  these  they  are  found  in  almost  100  per  cent,  of  cases 
of  rabies.  They  have  also  been  found  in  the  human  subject 
in  a  very  large  percentage  of  cases,  and  have  not  been 
identified  in  any  other  condition.  But  although  their  presence 
was  considered  pathognomonic  of  the  disease,  their  aetiological 
relationship  to  it  was  not  established  until  in  1912  Noguchi, 
using  similar  cultural  methods  to  those  found  successful  for 
the  spirochaetes  of  syphilis  and  relapsing  fever,  cultivated 
from  the  brains  and  spinal  cords  of  infected  animals 
"  very  minute  granular  and  coarser  pleomorphic  chromatoid 
bodies  transferable  through  many  generations."  On  four 
occasions  in  these  cultures  nucleated  round  or  oval  bodies 
surrounded  with  membranes,  similar  in  appearance  to  the 
Negri  bodies  of  the  brain,  appeared  suddenly  in  the  cultures 
and  lasted  for  from  four  to  five  days.  He  also  produced 
rabies  experimentally  by  inoculation  of  either  form  of  culture 
into  dogs,  rabbits  and  guinea-pigs. 

It  was  known  previously  that  the  virus  could  pass  through 
coarse  Berkefeld  filters,  and  this  militated  against  the  view 
that  the  Negri  bodies  were  the  cause  of  the  disease.  Recent 
workers  consider,  however,  that  these  are  either  a  phase  in  the 
life  cycle  of  a  filter-passing  organism,  or  are,  in  part,  constituted 
by  the  reaction  of  the  tissues  to  the  presence  of  the  organism. 


RABIES  219 

Noguchi's  results  suggest  that  the  former  view  is  the  more 
correct. 

Pathology. — The  virus  of  the  disease  seems  to  reach  the 
nervous  system  along  the  nerve  trunks  after  being  absorbed 
by  the  fine  terminal  filaments  of  the  nerves,  and  for  this  reason 
the  incubation  period  varies  with  the  distance  of  the  point  of 
inoculation  from  the  nervous  centres.  Thus,  inoculations  into 
the  anterior  chamber  of  the  eye  or  under  the  dura  mater  bring 
on  a  very  acute  attack  of  the  disease  after  a  minimal  incubation 
period.  Infection  may  also  take  place  from  a  healthy  mucous 
membrane,  such  as  the  conjunctival  or  nasal.  As  regards  the 
path  whereby  the  poison  reaches  the  higher  nervous  centres, 
experiments  seem  to  prove  that  it  travels  up  the  cord  in  the 
same  way  as  tetanus.  It  seems  also  to  extend  into  the 
nerves  of  the  opposite  limb,  but  this  may  be  part  of  the  general 
diffusion  of  the  virus  throughout  the  body. 

The  virus  is  excreted  by  most  of  the  glands  of  the  body, 
perhaps  chiefly  by  the  parotid,  and  it  has  been  found  in  the 
secretions  from  the  lachrymal  and  mammary  glands  and  the 
pancreas.  It  is  found  in  all  parts  of  the  nervous  system,  in- 
cluding the  cerebro-spinal  fluid,  the  sympathetic  nervous  system 
and  the  suprarenal  glands. 

A  great  deal  of  experimental  work  has  been  done  on  the 
variations  in  the  toxicity  of  the  virus.  Thus,  the  passage  of 
cerebro-spinal  fluid  through  a  series  of  monkeys  attenuates  the 
virus,  whereas  passage  through  rabbits  increases  the  toxicity. 
With  dogs  it  remains  fairly  constant.  Exposure  to  light  and 
air  diminishes  its  strength,  and  it  is  destroyed  by  heating  to 
50°  C.  for  an  hour,  or  to  60°  C.  for  half  an  hour,  and  by  most 
antiseptics  in  weak  solutions.  Pasteur  passed  the  virus  through 
rabbits  until  the  incubation  period  was  reduced  to  six  or 
seven  days.  Beyond  this  he  could  not  raise  the  toxicity,  and 
he  called  this  the  "  virus  fixe."  Starting  then  with  the  cords 
of  rabbits  of  this  maximum  toxicity,  he  found  that  storage  in 
sterile  flasks  over  some  hygroscopic  material  gradually  reduced 
the  toxicity  until  after  fourteen  days  of  storage  inoculations 
no  longer  produced  the  disease.  From  this  basis  he  started 
preventive  inoculations,  giving  injections  of  rabbit's  cord,  at 
first  inactive,  then  gradually  more  and  more  potent,  until  cords 
containing  the  "  virus  fixe  "  were  given.     He  found  that  if  this 


220  RABIES 

treatment  were  commenced  within  five  days  of  the  bite  nearly 
100  per  cent,  of  cases  failed  to  develop  the  disease,  and  even 
later  a  large  proportion  could  be  saved. 

Sometimes  transient  paraplegia  supervenes  after  the  eighth 
day  of  treatment,  but  this  usually  passes  off  in  four  to  five  days. 
The  cause  of  this  is  unknown,  but  it  may  be  that  during  the 
process  of  destruction  of  the  virus  by  the  cells  of  the  body 
some  toxin  is  set  free  which  has  a  selective  action  on  the  cells 
of  the  central  nervous  system. 

Morbid  anatomy. — The  naked-eye  appearances  of  the  brain 
and  cord  show  nothing  characteristic  of  the  disease.  General 
congestion  of  the  grey  matter  of  the  cord,  and  medulla,  is 
present,  and  frequently  small  haemorrhages  are  to  be  seen, 
most  commonly  in  the  floor  of  the  fourth  ventricle.  The 
incidence  of  the  disease  seems  to  fall  chiefly  on  the  medulla, 
then  on  the  cord,  and  least  on  the  cortex  and  central 
ganglia. 

Microscopically,  the  most  obvious  change  in  the  infected 
region  is  infiltration  of  the  perivascular  adventitial  spaces 
with  small  round  cells.  There  is  also  considerable  glial  pro- 
liferation, and  in  the  most  affected  areas  the  ganglion  nerve 
cells  are  surrounded  with  a  ring  of  parasitic  glia  cells.  The 
nerve  cells  themselves  undergo  considerable  degenerative 
changes,  being  swollen  and  containing  hyaline  bodies  near  the 
nucleus.  Negri's  bodies  may  be  found  in  them  with  appropriate 
staining  methods.  Golgi  has  described  alterations  in  the 
dendrites,  which  are  diffusely  swollen  or  show  small  swellings 
along  their  stems.  This  change  is  diffusely  spread  throughout 
the  cortex.  In  the  nerves  along  wjiich  the  infection  has  run 
degenerative  changes  are  often  found,  such  as  breaking  up  of 
the  myelin,  swelling  of  the  axons,  and  small-celled  infiltration. 
The  salivary  glands  show  accumulations  of  leucocytes  and 
vascular  congestion. 

REFERENCES 

MacCallum,  W.  G.  :  Textbook  of  Pathology,  1919. 
MuiR,  R.,  AND  Ritchie,  J.:  Manual  of  Bacteriology,  1919. 
Nageotte,    J.,   AND   RiCHE,    A.!   Coriiil  and   Ranvier,   Man.   d'histol.   Path. 
Paris,  1907,  vol.  iii. 

Landry's"  Paralysis. 

Buzzard,  E.  F.:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910, 
p.  670, 


INFFXTIVE  DISEASES  221 

Acute  Poliomyelitis. 
Batten,  F.  E.:  Lumleian  Lectures.     Brain,  1916,  vol.  xxxix. 

Herpes  Zoster. 
Head,  Henry:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,   1910, 
p.  470. 

Trypanosomiasis. 

MoTT,  F.  W.:  Archives  of  Neurol. ,  1907,  vol.  iii.,  p.  581. 
Muir,  R.,  and  Ritchie,  J.:  Manual  of  Bacteriology,  1919. 

Tetanus. 
CouRTOis-SuFFiT  AND  GiROUS  I  Lcs  formcs  anormaUs  du  Tetanos.     Paris,  1916. 
Muir,  R.,  and  Ritchie,  J.:  Manual  of  Bacteriology,  1919- 

Teale,  F.  H.,  and  Embleton,  D.:  Journ  of  Path,  and  Bad.,  1919,  vol.  xxiii., 
P-  50. 

Chorea. 
PoYNTON  and  Paine:  Rheumatism.     London,  1914. 

Rabies. 

Muir,  R.,  and  Ritchie,  J.:  Manual  of  Bacteriology,  1919- 
NoGUCHi,  H.:  Journ.  of  Exper.  Med.,  1913,  xviii.,  p.  314. 

Lethargic  Encephalitis. 

Buzzard,  E.  F.,  and  Greenfield,  J.  G. :  Brain,  iqiq,  vol.  xlii..  p.  305. 
McIntosh,  J.,  AND  TuRNBULL,  H.  M. :  British  Journ.  of  Exper.  Pathology. 

London,  1920,  vol.  i.,  p.  89. 
Marinesco  AND  McIntosh,  J. :  Report  to  the  Local  Government  Board.     No.  121, 

1918. 
Netter,  A.:  Bull,  de  I' Acad,  de  Med.,  1918.     T.  Ixxix.,  p.  337. 


CHAPTER  VII 
EFFECTS  OF  POISONS 

I.  Neuritis. 

The  term  neuritis  is  applied  both  to  inflammations  of  the 
nerves  and  to  certain  degenerative  processes  which  affect  the 
nerve  fibres,  without  producing  any  inflammatory  reaction  in 
the  tissues  surrounding  them.  Any  of  the  constituent  parts 
of  a  nerve  fibre  may  be  primarily  and  chiefly  affected.  Thus, 
the  connective  tissue  of  the  peri-  or  endo-neurium  may  undergo 
the  greatest  change,  the  vessels  may  be  little  or  much  congested, 
or  the  nerve  fibres  themselves  may  degenerate  from  a  toxic 
cause  with  little  or  no  reaction  in  the  supporting  structures. 
For  the  most  part,  however,  all  these  structures  are  affected 
at  the  same  time  to  a  greater  or  less  degree,  but  as  certain 
elements  tend  to  be  specially  damaged  by  certain  causes,  two 
main  groups  of  neuritis  are  distinguished,  the  interstitial  and 
the  parenchymatous.  Interstitial  neuritis  is  always  asym- 
metrical. It  is  usually  localised,  but  may  spread  along  a 
nerve.  Parenchymatous  neuritis,  on  the  other  hand,  is  usually 
symmetrical.  It  tends  to  affect  chiefly  the  peripheral  portions 
of  the  nerves,  and  may  affect  many  nerves  throughout  the 
body,  both  cranial  and  spinal,  when  it  is  termed  "  multiple 
peripheral  neuritis." 

Aetiology. — In  general  it  may  be  said  that  interstitial  neuritis 
is  due  to  lymph-borne  or  local  causes,  parenchymatous  neuritis 
to  blood-borne  or  general  causes.  In  both  cases  the  general 
resistance  of  the  patient  plays  a  great  part.  A  rheumatic  or 
gouty  diathesis  predisposes  to  local  nerve  inflammations, 
and  tuberculosis,  diabetes,  and  blood  diseases  lower  the 
resistance  to  general  toxins  and  lead  to  multiple  neuritis.  At 
the  same  time,  the  attack  tends  to  be  more  severe  and  the 
recovery  more  prolonged  in  debilitated  than  in  strong,  healthy 
subjects. 

222 


NEURITIS  223 

Interstitial  neuritis  may  be  more  directly  caused  by  exposure 
to  cold,  by  prolonged  or  intermittent  pressure  on  a  nerve, 
or  by  the  proximity  of  some  infective  focus,  such  as  an 
abscess,  a  superficial  sore,  a  diseased  joint  or  an  unhealthy 
mucous  membrane.  In  the  first  two  cases  the  process  is  an 
aseptic  one  and  is  usually  localised  and  quickly  recovered 
from.  In  infective  cases,  on  the  other  hand,  the  inflammation 
may  spread  up  the  nerve,  affecting  other  nerves  of  the  plexus, 
and  may  reach  the  spinal  cord,  causing  myelitis  {ex  neuritide) . 
The  recovery  depends  on  the  immunity  of  the  patient  and  the 
removal  of  the  cause.  It  may  be  extremely  prolonged,  so  that 
in  some  cases  surgical  intervention  has  been  needed  to  end 
what  appeared  to  be  interminable  suffering. 

Parenchymatous  neuritis  is  due  to  chemical  or  microbic 
poisons,  of  which  the  commonest  are  lead,  alcohol  and  the 
diphtheria  toxin.     Of  the  others  we  must  note : 

(i)  Inorganic  :  arsenic,  mercury,  phosphorus  and  silver. 

(2)  Organic :  ether,  bisulphide  of  carbon,  dinitro-benzol, 
aniline,  carbon  monoxide. 

(3)  Toxins  of  various  bacteria,  especially  those  of  influenza, 
enteric,  pneumonia,  erysipelas,  gonorrhoea,  septicaemia  of 
all  kinds  and  malaria. 

Syphilis  also  is  said  to  give  rise  to  peripheral  parenchymatous 
neuritis,  or  at  least  to  aid  in  its  causation.  In  addition,  we 
must  confess  that  many  cases  of  peripheral  neuritis  occur 
which,  in  the  absence  of  any  known  cause,  we  are  forced  to 
attribute  to  some  unknown  toxin. 

Recent  work  has  thrown  doubt  on  the  role  of  alcohol  as  a 
direct  cause  of  parenchymatous  neuritis,  and  certain  observers 
prefer  to  consider  that  it  plays  a  similar  part  to  tuberculosis 
and  diabetes  in  being  merely  a  predisposing  cause  or  in  so 
altering  tissue  metabolism  that  the  nerves  become  an  easy 
prey  to  other  toxins. 

Morbid  anatomy — (i)  Interstitial  form. — On  removal  from  the 
body  the  affected  nerve  is  swollen,  often  irregularly,  along  a 
portion  of  its  course.  In  the  early  stages  of  the  disease  it  is 
soft,  hyperaemic,  and  may  contain  lymph  between  its  bundles. 
In  the  later  stages  it  becomes  firmer  from  overgrowth  of  fibrous 
tissue. 

On   microscopic    examination    the   peri-    and  endo-neural 


224  EFFECTS  OF  POISONS 

sheaths  show  a  greater  or  less  degree  of  infiltration  with  round 
cells,  and  proliferation  of  the  connective  tissue  and  endothelial 
cells  with  the  production  of  phagocytes.  The  vessels  are  con- 
gested and  their  walls  filled  with  cells  of  various  kinds.  There 
may  be  some  exudation  of  lymph  which  is  in  process  of 
organisation.  As  we  pass  toward  a  later  stage  connective-tissue 
overgrowth  assumes  the  chief  role,  and  the  cellular  infiltration 
becomes  less  marked.  The  nerve  fibres  themselves  may  be 
pressed  on  by  lymph  or  overgrown  fibrous  tissue  and  undergo 
changes  similar  to  those  in  parenchymatous  neuritis.  But 
although  there  is  degeneration  of  the  medullary  sheaths  of 
the  nerves,  the  axons  tend  to  persist,  and  thus  function  is  not 
greatly  affected  and  is  quickly  restored.  Complete  recovery  in 
interstitial  neuritis  may  be  rapid  when  the  inflammatory 
products  are  completely  removed,  or  it  may  be  more 
prolonged  when  organisation  of  the  exudate  and  connective- 
tissue  hyperplasia  has  occurred.  In  such  cases  the  thickening 
of  the  nerve  may  be  permanent,  and  fibrous  tissue  overgrowth 
may  affect  its  whole  course  and  even  its  ganglion. 

Pathologically  it  is  difficult  if  not  impossible  to  distinguish 
between  the  slighter  affections  of  nerves  which  are  grouped 
under  the  term  "  neuralgia  "  and  severer  cases  where  the  nerves 
are  more  markedly  affected.  It  has  been  shown  in  cases  of 
death  from  cancer  of  the  tongue,  bed-sores,  abscesses,  etc., 
that  the  nerves  in  relation  to  these  foci  are  infiltrated  with  in- 
flammatory products  among  which  organisms  have  been  found. 
It  therefore  seems  likely  that  certain  cases  of  neuralgia 
and  referred  pain  in  connection  with  some  such  inflammatory 
focus  are  due  to  true  inflammation  of  the  nerve  sheaths.  Thus, 
in  trigeminal  neuralgia  a  fibrous  overgrowth  in  and  around  the 
Gasserian  ganglion  is  the  usual  pathological  picture. 

(2)  Parenchymatous  neuritis. — While  the  various  poisons 
which  produce  this  condition  vary  to  some  extent  in  their 
mode  of  attack  on  the  nerves,  certain  pathological  results  are 
common  to  all. 

I.  The  nerves  tend  to  be  more  affected  at  their  periphery 
than  at  their  emergence  from  the  spinal  canal.  In  fact,  nerves 
which  are  severely  affected  may  show  little  change  at  the  level 
of  the  plexus  from  which  they  spring.  The  degree  to  which 
this  is  true  varies  with  the  causal  toxin.     Alcohol  affects  the 


NEURITIS  225 

terminal  fibres  of  the  nerves,  especially  their  fine  intermuscular 
branches.  Diphtheria  and  lead  affect  the  nerve  fibres  more 
evenly.  But  all  forms  of  parenchymatous  neuritis  assume 
this  peripheral  distribution,  and  are  therefore  often  termed 
"  multiple  peripheral  neuritis." 

2.  The  most  obvious  changes  are  found  in  the  medullary 
sheath.  The  axis  cylinders  also  suffer,  sometimes  very  severely, 
and  the  cells  of  the  sheath  of  Schwann  undergo  great  change. 
But  while  preparations  stained  for  the  medullary  sheath  may 
show  a  great  degree  of  degeneration,  investigation  by  Biel- 
schowsky's  stain  for  axis  cylinders  may  show  comparatively 
little  destruction  of  these  elements. 

On  examination  of  an  affected  nerve  in  Marchi  prepara- 
tions the  degenerated  fibres  appear  as  chains  of  black  dots, 
representing  globules  of  fat  formed  by  the  breaking  down  of 
the  myelin.  At  first  these  are  of  small  size  and  are  massed 
irregularly  within  the  neurolemmal  sheath.  Darkly  staining 
globules  are  also  seen  inside  the  cells  of  the  sheath  of 
Schwann,  in  cells  lying  within  this  sheath  which  are  probably 
derived  from  it,  and  in  phagocytic  mesodermal  cells  which 
lie  among  the  nerve  fibres.  The  affected  nerve  fibres  are 
irregular  in  outline,  and  in  later  stages  many  are  shrunken. 
Preparations  stained  for  cellular  reaction,  as  by  haematoxylin, 
polychrome  methylene  blue  or  thionin  blue,  show  prolifera- 
tion of  the  cells  of  the  sheath  of  Schwann  and,  to  a  greater 
or  less  extent,  of  the  connective  tissue  and  other  meso- 
dermal elements  surrounding  the  nerve  fibres.  Many  of  the 
cells  of  the  neurolemma  assume  phagocytic  and,  it  may 
be,  migratory  powers,  and  are  found  filled  with  degeneration 
products  lying  free  within  the  sheath.  Scharlach  R.  and  other 
fat  stains  show  that  these  products  are  largely  composed  of 
fully  formed  fat,  while  others  are  fatty  acids,  and  in  the  later 
stages  cholesterin-containing  substances  also  appear,  chiefly 
in  the  mesodermal  phagocytes.  A  comparison  of  these  re- 
actions with  those  which  take  place  in  degenerations  of  the 
brain  and  spinal  cord  shows  that  the  cells  of  the  sheath  of 
Schwann  take  a  similar  part  in  fat  synthesis  from  degenerated 
myelin  to  that  taken  by  their  analogues,  the  neuroglia  cells  of 
the  central  nervous  system  (p.  22). 

Bielschowsky's  silver  impregnation  method  shows  that  the 

15 


226  TOXIC  MYELITIS 

axis  cylinders  do  not  undergo  any  great  destruction.  In 
the  less  affected  nerve  fibres  the  axis  cylinders  do  not 
differ  to  any  great  extent  from  the  normal.  In  more 
affected  fibres  they  are  in  a  state  of  granular  degeneration. 
Other  nerve  fibres  contain  one  or  more  fine  fibrils  studded 
with  spindle-shaped  or  globular  varicosities,  and  either  running 
a  straight  or  wavy  course  or  twisting  round  one  another  in 
spiral  form.  These  probably  represent  regenerated  fibres; 
and  it  appears  that  regeneration  of  axons  often  takes  place 
rapidly  at  an  early  stage  in  peripheral  neuritis.  The  investment 
with  medullary  sheath  which  is  necessary  for  restoration  of 
function  may,  however,  be  delayed  until  the  poison  causing 
the  disease  has  ceased  to  act. 

2.  Toxic  Myelitis. 

This  rare  form  of  myelitis  differs  from  the  infective  type  in 
its  less  acute  onset  and  course,  and  still  more  perhaps  in  the  fact 
that  recovery  is  more  frequently  complete.  Little  is  known  of 
its  aetiology,  except  in  those  cases  which  have  been  described 
as  associated  with  pregnancy  and  often  accompanied  by 
serious  disturbances  in  the  functions  of  the  heart  and  kidneys. 
The  close  relationship  between  child-bearing  and  this  form  of 
myelitis  is  shown  by  the  improvement  in  the  latter  after  con- 
finement, and  by  its  recurrence  in  subsequent  pregnancies. 

Morbid  anatomy. — Gross  changes  are  not  very  obvious,  but 
some  oedema  and  slight  softening  of  the  spinal  tissues  may 
be  observed.  Microscopically,  the  chief  changes  consist  in 
swelling  of  the  myelin  sheaths  and  of  the  axis  cylinder  processes, 
especially  in  the  white  matter.  The  change  is  generally  patchy 
in  distribution,  and  does  not  affect  systems  as  a  whole.  In 
addition,  there  are  toxic  changes  in  the  nerve  cells  and  in  the 
neuroglia,  although  the  latter  do  not  show  the  proliferation 
which  is  characteristic  of  the  infective  form.  The  Marchi  stain 
demonstrates  fatty  changes  in  the  myelin  sheaths,  and  the 
Nissl  stain  illustrates  the  changes  in  the  ganglion  cells.  Owing 
to  the  fact  that  recovery  is  the  rule  rather  than  the  exception, 
the  opportunities  for  studying  this  form  of  myelitis  have  not 
been  frequent. 


EFFECTS  OF  POISONS  227 

3.  Encephalopathy  (Effects  of  Poisons  on  the  Brain). 

Various  organic  and  inorganic  chemical  substances  have 
long  been  known  to  have  definite  actions  on  the  brain,  some 
affecting  primarily  the  higher  centres,  others  the  vital  mechanism 
of  the  medulla  oblongata.  For  this  knowledge  we  are  chiefly 
indebted  to  the  experimental  work  of  pharmacologists,  and 
as  a  result  our  knowledge  of  the  direct  action  of  the  poisons 
rests  on  a  firmer  basis  than  that  of  the  remoter  effects  produced 
when  the  poison  is  absorbed  in  smaller  doses  over  a  longer 
period.  These  changes  result  from  faulty  nutrition  of  the 
nerve  cells  and  their  processes  and  may  be  directly  due  to 
the  prolonged  action  of  the  poison,  or  may  be  caused  indirectly 
by  changes  in  the  walls  of  the  blood  vessels. 

The  commonest  poison  to  exert  a  noxious  effect  on  the  brain 
is  ethyl  alcohol.  Some  of  the  well-known  results  of  excessive 
indulgence  in  this  drug  are  due  to  its  direct  action  on  the  nerve 
cells  and  fibres  when  taken  in  an  overdose.  Others,  not  so 
well  understood,  seem  to  be  due  to  prolonged  use  of  alcohol 
in  smaller  quantities.  And  here  we  must  also  reckon  with  the 
effects  of  changes  in  metabolism  induced  by  the  drug,  which 
seem  to  have  a  considerable  bearing  on  the  aetiology  of 
delirium  tremens.  In  the  polyneuritic  psychosis  we  seem  to  be 
dealing  with  the  chronic  direct  poisoning  of  nerve  cells  and  their 
processes  throughout  the  nervous  system.  In  this  condition 
Ballet  has  described  changes  in  the  pyramidal  cells  of  the 
cortex  consisting  of  swelling  and  vacuolation  of  the  cytoplasm 
along  with  perinuclear  chromatolysis  and  displacement  of 
the  nucleus.  Degeneration  of  the  tangential  and  supraradial 
systems  of  fibres  in  the  cortex  has  also  been  found.  These 
lesions  are  not  constant,  and  it  is  noticeable  that  the  symptoms 
are  much  more  pronounced  than  would  be  suggested  by  the 
pathological  changes  which  have  been  described.  On  the 
other  hand,  in  the  accompanying  peripheral  neuritis  extensive 
pathological  changes  are  found  even  when  the  symptoms  are 
minimal.  It  is  probable  that  in  both  cases  the  underlying 
pathological  basis  is  the  same,  viz.  a  chronic  intoxication 
resulting  in  failure  of  nutrition  of  nervous  elements. 

In  chronic  alcoholic  insanity  the  pathological  changes  are 
very  various,  and  many  of  them  appear  to  be  due  to  degenera- 


228  LEAD  ENCEPHALOPATHY 

tion  of  the  blood  vessels  of  the  brain,  which  is  the  only  constant 
feature.  They  consist  of  diffuse  sclerosis  of  the  cerebral  cortex 
with  widening  of  the  sulci  and  shrinkage  of  the  brain  substance. 
"  Pachymeningitis  interna  haemorrhagica  "  is  often  associated 
with  this  disease. 

In  the  more  acute  cases  of  lead  poisoning  convulsions  fre- 
quently occur,  and  they  may  be  associated  with  optic  neuritis. 
In  fatal  cases  of  this  kind  the  brain  is  found  to  be  pale  and  oede- 
matous,  with  an  excess  of  fluid  in  the  meshes  of  the  arachnoid. 
These  changes  appear  to  be  due  to  spasm  of  the  cerebral  arteries 
and  diminution  of  the  blood  supply  to  the  brain.  In  a  case  of 
chronic  lead  poisoning  Mott  found  increase  of  connective  tissue 
in  the  pia-arachnoid  and  the  walls  of  the  small  vessels,  but  no 
evidence  of  small  cell  infiltration.  Occasional  haemorrhages 
into  the  perivascular  sheath  were  seen,  and  adherent  to  the 
outermost  layer  of  the  vessels  were  large  fibre-forming  glial 
cells.  The  glia  was  everywhere  undergoing  proliferation  with 
formation  of  new  fibres,  especially  in  the  superficial  and  deep 
layers  of  the  cortex,  where  the  glial  increase  was  out  of  pro- 
portion to  the  wasting  of  the  neural  elements.  Under  the  pia 
also  the  glia  was  very  dense.  The  Betz  cells  of  the  motor  cortex 
were  degenerated,  showing  perinuclear  chromatolysis  and  some 
neuronophagy,  as  well  as  pigmentary  changes,  but  there  was  no 
gross  atrophy  or  degeneration  of  the  fibres  of  the  cortex  or  of 
the  pyramidal  tract,  except  a  slight  diffuse  sclerosis  of  the 
latter  in  the  lumbar  region. 

Some  cases  of  arsenical  neuritis  develop  a  similar  condition 
to  the  polyneuritic  psychosis  of  chronic  alcoholism.  Optic 
atrophy  has  been  observed  to  follow  the  administration  of  large 
doses  of  arsenical  compounds,  such  as  atoxyl.  It  may  also 
result  from  poisoning  by  methyl-alcohol  and  quinine. 

Carbon  monoxide  has  both  direct  and  indirect  actions  on  the 
brain.  Its  direct  action  on  the  nerve  cells  may  be  explained 
by  its  power  of  combining  with  the  haemoglobin  of  the  blood 
and  thus  depriving  the  brain  of  its  supply  of  oxygen.  In 
addition  to  this  action  on  the  nerve  cells,  small  perivascular 
haemorrhages  have  been  found  in  the  white  matter  of  the 
brain,  and  these  may  account  for  certain  nervous  symptoms, 
such  as  the  partial  paralysis  remaining  after  the  immediate 
effects  of  the  poison  have  passed  off. 


EFFECTS   OF  POISONS  229 

4.  Ergotism. 

This  disease,  though  rare  in  England,  has  occurred  in 
the  form  of  severe  epidemics  on  the  Continent,  especially 
in  France.  But  since,  in  the  seventeenth  century,  it  was 
proved  to  be  due  to  the  common  fungus  of  rye,  "  ergot  of 
rye,"  the  disease  has  seldom  appeared  in  epidemic  form  in 
civilised  communities,  although  it  is  endemic  in  parts  of  Russia. 
Its  two  forms,  the  convulsive  and  the  gangrenous,  seem 
usually  to  occur  in  separate  epidemics.  Localities  where  one 
is  prevalent  seem  to  be  immune  from  the  other. 

Aetiology. — Although  the  cause  of  the  disease  has  been 
known  for  more  than  two  centuries,  certain  points  in  connection 
with  the  aetiology  have  not  been  entirely  cleared  up.  Thus, 
it  is  known  that  ergot  grown  in  certain  localities  and  under 
certain  conditions  is  more  toxic  than  that  grown  elsewhere, 
and  that  ergot  grown  medicinally  in  this  country  is  compara- 
tively inert,  but  the  exact  conditions  of  growth  favourable  to 
the  production  of  poisonous  active  principles  are  not  known. 
These  may  lie  in  the  nature  of  the  soil  or  in  conditions  of 
moisture,  heat,  etc.,  in  the  climate.  It  is  known  that  foggy 
fen  country  is  most  liable  to  epidemics  of  ergotism,  especially 
when  there  has  been  a  hot  summer.  Conditions  of  poverty 
and  destitution  in  the  community  and  individual  susceptibility 
play  a  great  part  in  the  incidence  of  the  disease. 

Pharmacological  research  has  shown  that  ergot  contains  three 
active  principles  which  have  not  been  isolated  in  crystallisable 
form,  and  which  may  be  combinations  of  one  or  more  active 
principles  with  more  inert  substances.  These  active  principles 
have  been  called  (i)  ergotinic  acid,  (2)  cornutine,  and  (3)  spha- 
celinic  acid.  The  first  does  not  appear  to  have  any  direct 
relationship  with  the  disease.  Cornutine  has  an  action  on  the 
medullary  centres  and  may  produce  clonic  convulsions.  To 
its  action  the  convulsive  type  of  ergotism  is  probably  due. 
Sphacelinic  acid  has  a  constrictor  action  on  plain  muscle 
fibre,  especially  on  that  of  the  vessel  walls.  This  takes  effect 
through  the  sympathetic  nerves,  as  perfusion  of  isolated  vessels 
with  extracts  of  ergot  has  no  effect  in  diminishing  the  calibre 
of  the  vessels. 

Ergotism  is  thus  due  to  the  direct  action  on  the  nervous 


230  EFFECTS  OF  POISONS 

system  of  one  or  other  of  these  two  poisons,  cornutine  and 
sphaceUnic  acid.  Whether  the  symptoms  are  those  of  the 
convulsive  type  or  the  gangrenous  type  is  probably  due  to  the 
relative  amounts  of  the  two  poisons  present  in  the  grain  causing 
the  epidemic.  Individual  susceptibility  may  also  play  a  part, 
but  that  it  is  a  small  one  is  indicated  by  the  way  in  which 
epidemics  are  limited  to  one  form. 

Pathology. — A  very  constant  feature  of  the  disease  is  degenera- 
tive change  in  the  cord.  This  is  similar  to  that  seen  in  pellagra, 
except  that,  being  less  chronic,  there  is  less  sclerosis,  and  more 
evidence  of  recent  destruction  of  nerve  fibres.  The  long 
columns  of  the  cord  suffer  most,  especially  the  dorsal 
columns.  The  resemblance  to  the  degeneration  of  tabes  may^ 
be  very  close  in  sections  stained  for  myelin,  but  a  more 
minute  examination  with  other  tissue  stains  shows  that  this 
resemblance  is  only  superficial,  and  that  the  lesion  is  not 
really  systematised.  Some  degeneration  of  the  sensory  nerves 
has  also  been  described. 

The  arteries  show  thickening  of  their  middle  coat  and  hyaline 
changes  of  the  intima.  The  smaller  arterioles  are  thrombosed. 
Congestive  changes  in  the  lungs  are  very  common. 

5.  Pellagra. 

Definition. — Pellagra  is  a  disease  which  occurs  sporadic- 
ally or  in  endemic  form.  It  has  long  existed  in  the  north  of 
Italy,  and  recently  has  spread  in  the  Southern  States  of  North 
America.  It  is  characterised  by  cutaneous  eruptions,  gastro- 
intestinal disturbances,  and  a  tendency  to  degeneration  of  the 
nervous  system. 

Aetiology. — The  causation  of  this  disease  is  still  obscure. 
For  long  it  has  been  known  to  attack  communities  where  maize 
is  the  staple  article  of  diet,  and  where  general  poverty  exists. 
The  common  occurrence  of  the  disease  in  spring,  and  its 
similarity  to  ergotism  as  regards  pathological  changes,  led  to 
the  view  that  it  was  due  to  the  growth  of  some  mould  or  fungus 
on  maize.  Many  cases  have,  however,  occurred  in  which  maize 
could  with  certainty  be  ruled  out  of  court  as  a  causative  factor. 
More  recent  work  has  indicated  that  pellagra  is  a  deficiency 
disease  due  to  a  diet  in  which  the  proteids  are  small  in  quantity 
and  of  poor  quality.     It  has  been  shown  that  proteids  vary 


PELLAGRA  231 

greatly  in  their  value  as  foodstuffs,  and  that  those  derived  from 
the  seeds  of  plants  are  far  inferior  to  animal  proteids  in  their 
power  of  maintaining  nitrogenous  equilibrium.  This  is  attri- 
buted, among  other  things,  to  their  poverty  in  tryptophan  and 
lysine.  Goldberger,  in  1914,  was  able  to  reproduce  pellagra 
in  prisoners  by  feeding  them  on  diets  similar  to  those  consumed 
in  pellagrous  districts.  These  diets  have  been  shown  to  be 
composed  largely  of  the  seeds  of  plants,  such  as  maize,  beans, 
and  rice,  the  proteids  of  which  have  a  low  biological  value. 

Morbid  anatomy. — Whatever  may  be  the  aetiological  agent, 
there  is  no  doubt  that  the  lesions  found  in  the  nervous  system 
are  of  a  toxic  character.  They  have  been  chiefly  studied  in 
the  spinal  cord,  but  the  nerves  and  the  brain  are  also 
affected. 

Macroscopically  no  marked  abnormality  is  seen  beyond  some 
slight  changes  in  the  dorsal  columns. 

Histologically  the  cord  shows  a  pseudo-systematised  lesion 
in  the  dorsal  columns.  In  the  cervical  region  the  column 
of  GoU  is  always  affected,  but  the  column  of  Burdach  may 
be  intact  or  show  irregular  bands  of  degeneration.  In  the 
thoracic  and  lumbar  regions  the  appearance  of  systematisation 
is  not  so  marked.  The  dorsal  root  zone  may  or  may  not  be 
involved,  and  the  cornu-commissural  zone  may  be  spared.  In 
fact  the  process  is  essentially  a  diffuse  one,  affecting  not  only 
the  dorsal,  but,  to  a  less  extent,  the  lateral  columns.  In 
the  latter  it  is  not  limited  to  the  pyramidal  tracts,  but  is 
spread  diffusely,  often  implicating  the  spino-cerebellar  tracts. 
Under  a  higher  power  of  the  microscope  the  picture  is  extremely 
like  that  seen  in  ^'  subacute  combined  degeneration,"  although 
the  changes  are  more  confined  to  the  dorsal  columns  and 
are  of  a  more  chronic  type.  Degeneration  of  myelin  is 
evidenced  by  the  numerous  granular  corpuscles  lying  in  the 
degenerated  areas  and  filling  the  adventitial  lymphatics  of 
the  veins.  Marchi's  stain  shows  that  these  are  filled  with  fat. 
Glial  proliferation  is  well  established,  both  amoeboid  glia  cells 
and  spider  cells  being  seen,  and  there  is  a  greater  formation 
of  new  glial  fibres  than  in  subacute  combined  degeneration. 
There  is  a  complete  absence  of  any  lymphocyte  or  plasma  cell 
infiltration. 

The  changes  in  the  nerve  cells  are  those  common  to  all 


232  EFFECTS  OF  POISONS 

subacute  toxic  diseases:  perinuclear  chromatolysis,  with 
eccentricity  of  the  nucleus  and  a  more  globular  outline  of  the 
cell  body.  The  cells  of  Clarke's  column  are  most  affected, 
but  the  ventral  horn  cells,  the  intermedio-lateral  tracts  and 
the  spinal  ganglion  cells  may  also  suffer.  Similar  changes  are 
found  in  the  Purkinje  cells  of  the  cerebellum,  in  the  cranial 
nerve  nuclei  and  in  the  pyramidal  cells  of  the  cortex. 

The  peripheral  nerves  have  been  studied  particularly  by 
Mario  Zalla  and  Kinnier  Wilson.  Changes  in  them,  although 
usually  slight  in  degree,  are  practically  constant.  Slight 
fragmentation  of  the  myelin  and  the  appearance  of  scattered 
droplets  staining  by  Marchi's  method  are  common.  The  axis 
cylinders  may  show  no  change,  or  only  slight  irregularities  of 
contour;  occasionally  the  axis  cylinders  may  split  up  into 
fibrils.  There  is  often  some  oedema  of  the  nerve  bundles  and 
thickening  of  the  interstitial  tissue.  Mario  Zalla  and  Wilson 
have  called  attention  to  the  great  increase  of  the  **  tt  granules 
of  Reich "  in  the  nerves  of  pellagrins.  These  are  small, 
irregularly-shaped  granules,  staining  metachromatically  and 
appearing  pinkish  when  coloured  with  thionin  blue.  They  are 
chiefly  seen  in  the  cells  of  the  sheath  of  Schwann,  but  may  be 
found  in  the  adventitia  of  blood  vessels.  Their  exact  nature 
is  not  yet  determined,  but  they  appear  to  be  a  form  of  degenera- 
tive product  of  nervous  matter. 

6.  Lathyrism. 

Aetiology. — This  is  a  paraplegia  of  fairly  rapid  onset  and 
tending  towards  cure,  which  is,  however,  never  complete.  It 
was  mentioned  by  Hippocrates,  and  in  more  recent  times  has 
occurred  in  France,  Italy  and  Algiers,  but  during  the  present 
century  it  has  been  confined  to  certain  parts  of  India. 

It  occurs  in  those  who  subsist  almost  entirely  on  a  diet  of 
pulse  [Lathyrus  sativus  or  L.  cicera).  It  is  probable  that  the 
grain  is  not  itself  toxic,  but  either  from  the  presence  of  some 
parasitic  fungus  (cf .  ergotism) ,  or  from  lack  of  some  constituent 
necessary  to  life  (cf.  beri-beri),  its  too  exclusive  use  leads  to  the 
disease.  In  India  it  is  to  be  noted  that  lathyrism  only  occurs 
during  famine  years,  when,  in  addition  to  the  shortage  of  other 
foods,  there  is  general  poverty,  and  that  its  incidence  is  confined 
to  the  rainy  season;    also  that  it   attacks  men  much  more 


LATHYRISM 


233 


Fig.  68. 
The  cord  in  a  case  of  lathyrism  stained  by  the  Weigert-Pal  method. 


234  EFFECTS  OF  POISONS 

frequently  than  women,  a  proportion  put  by  some  observers 
as  high  as  ten  men  to  one  woman  affected. 

Pathology. — We  have  only  had  the  opportunity  of  examining 
one  case  of  this  disease.  In  this  case  the  lesions  were  very 
similar  to  those  seen  in  ergotism,  i.e.  a  pseudo-systematised 
degeneration  of  the  long  ascending  and  descending  tracts  of 
the  cord.  This  was  particularly  marked  in  the  pyramidal 
tracts,  both  lateral  and  ventral,  in  the  direct  cerebellar  tracts, 
and  in  the  dorsal  columns.  In  the  lumbar  and  thoracic  regions 
the  margins  of  the  cord  showed  the  same  loose,  honeycombed 
structure  as  is  seen  in  the  more  rapid  cases  of  "  subacute  com- 
bined degeneration,"  with  oedema  at  the  point  of  entrance  of 
the  dorsal  roots.  The  nerve  roots  showed  a  definite  increase 
of  connective  tissue,  and  in  the  peripheral  nerves  a  similar 
increase  was  seen,  chiefly  in  the  epi-  and  peri-neurium.  These 
changes  are  all  of  the  same  character  as  those  found  in  ergotism, 
and  it  is  probable  that  the  two  diseases  are  closely  connected. 


7.  Beri-beri. 

This  disease  is  characterised  by  polyneuritis  or  anasarca 
or  both,  and  occurs  either  endemically,  chiefly  in  the  islands 
of  the  Indian  and  Pacific  Oceans,  or  in  epidemics.  It  is  not 
confined  to  the  human  race,  but  may  affect  several  species 
of  mammal  and  is  easily  produced  in  domestic  birds,  such  as 
pigeons  and  poultry. 

Aetiology. — Although  the  use  of  a  too  exclusive  diet  of  rice 
has  long  been  considered  to  be  the  cause  of  beri-beri,  it  is  only 
within  the  last  decade  that  the  exact  dietary  conditions 
necessary  to  produce  the  disease  have  been  worked  out.  It 
has  been  shown  that  an  "  accessory  factor  "  is  necessary  in  diets 
if  beri-beri  is  to  be  avoided,  and  that  the  addition  of  this 
substance  to  the  diet  of  patients  suffering  from  the  disease 
brings  about  a  rapid  cure.  This  factor  has  been  called  "  anti- 
neuritic  vitamine  "  or  "  water-soluble  B."  It  has  not  been 
isolated  in  a  pure  condition.  This  vitamine  is  present  in 
varying  amounts  in  most  natural  foodstuffs,  but  may  be 
removed  or  destroyed  by  the  artificial  measures  adopted  for 
their  preparation.  The  "  polishing  "  of  rice  and  the  milling  of 
wheat  to  a  white  flour  completely  remove  the  vitamine  whiQh 


BERI-BERI  235 

is  present  in  the  germ  and  aleurone  layer.  The  vitamine  is 
fairly  stable  at  ordinary  temperatures,  and  can  be  preserved 
in  the  dry  state  for  long  periods.  It  withstands  boiling  or 
steaming  at  100°  C,  but  rapidly  disappears  when  foodstuffs 
are  autoclaved  at  120°  C.  It  is  therefore  absent  from  most  forms 
of  tinned  food.  The  chief  sources  of  this  vitamine,  as  deter- 
mined by  experimental  work  on  pigeons,  are  rice  husks,  the  germ 
of  wheat  and  yeast.  It  is  also  present  in  fairly  large  amounts 
in  the  yolk  of  eggs,  in  ox-liver,  and  in  certain  cereals,  such  as 
linseed  and  lentils.  Small  amounts  are  present  in  milk,  fresh 
meat,  potatoes  and  other  vegetables.  Although  normally 
the  vitamine  is  present  in  milk,  nursing  women  who  are  suffering 
from  beri-beri  even  in  a  mild  form  may  transmit  the  disease 
to  their  infants  in  a  much  more  acute  form.  These  infantile 
cases,  which  are  always  of  the  dropsical  type,  are  rapidly  cured 
by  a  change  of  milk,  and  are  due  to  the  absence  of  the  anti- 
neuritic  vitamine  from  their  mother's  milk.  In  experimental 
work  on  poultry  the  disease  usually  commences  about  fourteen 
days  after  the  adoption  of  a  diet  from  which  the  anti- 
neuritic  vitamine  is  absent.  In  human  epidemics  the  time 
of  onset  has  been  shown  to  be  between  eighty  and  ninety 
days. 

It  is  to  be  noted  that  although  practically  any  diet  from 
which  the  "  water-soluble  B  "  vitamine  is  absent  will  produce 
the  disease  in  fowls  within  the  periods  stated,  yet  if  they  are 
deprived  of  everything  except  water,  they  survive  for  longer 
than  this  period  without  showing  any  signs  of  polyneuritis. 
This  and  the  similarity  of  the  neuritis  to  that  produced  by 
diphtheria  toxin  and  various  poisons  suggest  that  the  action  of 
the  vitamine  is  not  a  simple  nourishment  of  nerve  cells,  but 
that  it  neutralises  or  inhibits  the  action  of  some  poison  which 
is  produced  in  the  metabolism  of  carbohydrates.  The  onset 
of  the  disease  is  so  rapid  as  not  to  be  easily  explained  on  any 
simple  theory  of  deficiency  alone. 

The  disease  occurs  in  two  clinical  forms,  the  "  wet  "  charac- 
terised by  anasarca,  and  the  "  dry  "  characterised  by  paralysis 
and  wasting  of  the  limbs.  These  two  types  may  occur  together, 
and  in  the  "  wet  "  form  there  is  usually  a  certain  amount  of 
paralysis.  On  the  other  hand,  the  "  dry  "  form  usually  shows 
complete  lack  of  dropsical  symptoms. 


236  BERI-BERI 

Morbid  anatomy. — The  two  forms  differ  somewhat  in  their 
morbid  anatomy,  the  same  essential  lesions  being  present  but 
in  different  proportions.  Anasarca  and  hydropericardium 
are  present  in  the  wet  form,  along  with  congestion  of  the  spleen 
and  a  nutmeg  condition  of  the  liver.  In  all  fatal  cases  of  the 
disease  there  is  some  enlargement  of  the  right  side  of  the  heart, 
with  degeneration  of  the  heart  muscle.  This  may  take  the 
form  of  fatty  infiltration,  or  there  may  be  fragmentation  of 
the  muscle  fibres  with  loss  of  their  striation ;  or  again  there  may 
be  areas  from  which  the  muscle  fibres  have  completely  disap- 
peared, their  place  being  taken  by  connective  and  granulation 
tissues. 

The  essential  nervous  lesion  of  the  disease  appears  to  be  a 
multiple  neuritis,  which  has  been  found  in  every  case  examined 
to  this  end.  The  peripheral  nerves  of  the  limbs  may  be  healthy, 
when  there  is  degeneration  of  such  nerves  as  the  phrenic,  vagus, 
and  sympathetic  cardiac  plexus,  or  of  branches  of  the  solar 
plexus.  In  the  dry  form  there  is  always  some  polyneuritis  of 
the  limb  plexuses.  The  neuritis  is  of  the  pure  degenerative 
type,  without  any  alteration  in  the  connective-tissue  com- 
ponents of  the  nerves.  It  consists,  in  the  earlier  stages,  in 
slight  degeneration  of  the  myelin  sheaths,  with  the  appearance 
of  black  granules  by  Marchi's  stain.  Later  the  whole  medullary 
sheath  of  certain  nerve  fibres  may  become  broken  up  into  fatty 
globules,  without  any  obvious  change  in  the  axis  cylinders. 
At  a  still  more  advanced  stage  there  may  be  irregular  swelling 
and  fragmentation  of  the  axis  cylinders,  but  this  is  not  usual. 
These  changes  affect  only  a  small  proportion  of  the  nerve  fibres, 
but  those  which  show  degeneration  are  affected  throughout 
their  course.  Vedder  has  shown  that  the  earliest  changes  in  the 
nerve  affect  the  structure  of  the  neurokeratin  network.  In 
feeding  fowls  on  a  diet  of  polished  rice  he  found  changes  in  this 
structure  as  early  as  the  seventh  day,  before  any  symptoms  of 
paralysis  had  appeared. 

Along  with  the  changes  in  the  peripheral  nerves  there  are 
always  changes  in  the  ganglion  cells  of  the  brain-stem  and  cord. 
These  have  been  observed  especially  in  the  dorsal  root  ganglia 
and  in  the  motor  cells  of  the  ventral  horns  and  motor  cranial 
nerves.  They  consist  of  chromatolysis  affecting  first  the  Nissl 
granules  at  the  periphery  of  the  cell  along  with  vacuolation  of 


EFFECTS  OF  POISONS  237 

the  cytoplasm  and  collections  of  pigment  in  the  cell  body.  The 
cells  which  are  most  affected  may  be  swollen  and  globular 
and  contain  a  displaced  nucleus.  Degeneration  of  the 
dorsal  columns,  especially  the  tract  of  Goll,  has  been 
frequently  observed.  This  appears  to  be  secondary  to  the 
changes  in  the  cells  of  the  dorsal  root  ganglia,  and  is  not  so 
extensive  as  the  degeneration  in  the  corresponding  peripheral 
nerves.  Some  observers,  using  Marchi's  method,  have  found 
a  few  scattered  degenerated  fibres  in  all  the  tracts  of  the  cord. 
The  changes  in  the  muscles  are  of  the  neuritic  type  and  similar 
to  those  seen  in  other  forms  of  motor-nerve  palsy. 

Relationship  of  anatomical  changes  to  clinical  phenomena.— It 
has  been  frequently  observed  that  the  first  steps  in  the  cure 
of  the  paralysis  may  be  extremely  rapid,  a  few  days  of  altered 
diet  sufficing  to  get  the  patient  on  to  his  legs  again.  After  that 
it  may  be  weeks  or  months  before  he  regains  the  full  use  of  his 
limbs.  The  reason  for  this  lies  in  the  different  periods  required 
by  the  various  elements  affected  to  return  to  normal  functional 
activity ;  and  as  histological  changes  are  found  in  a  much  larger 
proportion  of  nerve  cells  than  of  myelin  sheaths,  it  is  justifiable 
to  assume  that  the  rapid  initial  recovery  is  due  to  resumption 
of  functional  activity  by  the  nerve  cells,  whereas  the  slower 
progress  towards  complete  cure  is  associated  with  the  remyeli- 
nation  of  peripheral  nerve  fibres.  In  the  present  state  of  our 
knowledge  it  is  impossible  to  say  whether  the  "  wet  "  form  of 
the  disease  is  due  primarily  to  degeneration  of  the  cardiac  plexus 
of  nerves,  to  primary  degeneration  of  the  heart  muscle,  or  to 
alterations  of  tissue  metabolism  favouring  oedema.  The 
evidence  seems,  on  the  whole,  to  be  against  the  nervous 
theory,  as  the  dropsy  comes  and  goes  without  any  change 
in  the  paralysis  of  the  limbs. 


REFERENCES 

Neuritis. 
Bury,  J.  S.:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910,  p.  415. 

Encephalopathy . 

MoTT,  F.  W. :  (Lead).  Arch,  of  Neurol.,  1909,  vol.  iv..  p.  117.  (Carbon 
Monoxide).  Proc.  Roy.  Soc.  of  Med.,  191 7,  vol.  x.;  Path.,  pp.  73-90; 
Arch,  of  Neurol.,  1907,  vol.  iii.,  p.  246. 

Oliver,  T.  :  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  ii.,  part  i,  p.  988. 


238  EFFECTS  OF  POISONS 

Ergotism. 

Allbutt,  T.  C:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  ii.,  part  i, 

p.  884. 
Nageotte,   J.,   AND   RiCHE,  A.  I  Comil    and  Ranvier,  Manuel  d'Hist.  Path., 

vol.  iii. 

Pellagra, 

Wilson,  S.  A.  K.:  Proc.  of  Roy.  Soc.  of  Med.,  1914,  vol.  vii.,  pp.  31-40. 

Beri-beri. 

Vedder,  E.  B.  :  Beri-beri.     London,  1913. 

See  also  Report  to  Med.  Research  Council  on  the  Present  State  of  Knowledge 

concerning  Accessory  Food  Factors  {Vitamines).     Special  Report  Series, 

No.  38,  1919. 


CHAPTER  VIII 
TUMOURS  OF  THE  BRAIN  AND  SPINAL  CORD 

A. — Tumours  of  the  Brain. 

It  is  customary  to  classify  under  tumours  of  the  brain  all 
forms  of  intracranial  new  growth ;  in  other  words,  all  forms  of 
tumour  which  tend,  by  increasing  the  cranial  contents,  to  affect 
the  functions  of  the  brain.  They  are  not  all,  strictly  speaking, 
tumours  of  the  brain  substance.  Some  of  them  are  metastatic, 
others  arise  from  the  vascular  connective  tissues,  others  from 
the  meninges,  and  others  from  the  cranial  bones.  Parasitic 
and  other  forms  of  cysts  are  also  included  among  brain  tumours 
on  account  of  the  similarity  of  the  symptoms  to  which  they 
give  rise. 

Tumours  of  the  brain  have  no  special  aetiology.  For  the  most 
part  their  origin  is  unknown,  except  in  the  case  of  the  parasitic 
and  metastatic  forms.  No  direct  relationship  to  trauma  has 
been  proved,  although,  as  in  other  parts  of  the  body,  there  are 
plenty  of  records  in  which,  as  a  by  no  means  surprising  coin- 
cidence, the  onset  of  symptoms  has  been  preceded  by  the 
history  of  some  more  or  less  trivial  injury.  In  this  connection 
it  is  perhaps  worth  remembering  that  the  more  severe  the  injury 
the  less  likely  does  it  appear  that  a  tumour  should  subsequently 
make  its  appearance.  Certain  forms  of  cysts,  simple  or  haemor- 
rhagic,  are  undoubtedly  of  traumatic  origin,  and  may  give  rise 
to  all  the  symptoms  of  a  new  growth. 

The  age  incidence  of  cerebral  tumours  do3s  not  altogether 
resemble  that  of  tumours  in  other  parts.  This  is  accounted 
for  in  part  by  the  fact  that  tuberculomata  and  syphilomata, 
growths  of  early  and  mid-life,  are  often  included  in  statistics, 
and  in  part  by  the  fact  that  gliomata,  one  of  the  commonest 
forms  of  cerebral  tumours,  are  more  prevalent  before  than  after 
forty-five  years  of  age.  It  must  be  remembered  also  that 
carcinomata,  so  frequently  the  cause  of  death  in  elderly  people, 

239 


240  TUMOURS  OF  THE  BRAIN 

are  comparatively  rare  in  the  brain,  and,  when  they  do  occur, 
are  almost  invariably  secondary  to  tumours  in  other  organs. 
Tumours  of  the  brain,  therefore,  are  comparatively  rare  in 
infancy  and  in  old  age,  but  common  enough  in  youth  and  middle 
life.  It  has  been  pointed  out  that  subtentorial  tumours  are 
more  common  in  early  life,  and  supratentorial  tumours  more 
common  in  adults,  but  this  is  probably  due  to  the  inclusion  of 
the  tuberculomata  of  the  cerebellum  and  pons  which  are  not 
infrequent  in  children.  Tumours  of  the  brain  are  more  common 
in  men  than  in  women. 

Glioma. 

This  form  of  neoplasm  rivals  syphilitic  gumma  and  tubercu- 
loma as  the  commonest  form  of  intracranial  tumour.  Gliomata 
are  diffuse  infiltrating  tumours  arising  from  glial  tissue.  They 
may  spread  among  the  nervous  elements  of  the  grey  or  white 
matter  of  the  brain,  and  attain  considerable  size  without  much 
destruction  of  nerve  cells  or  fibres.  While  they  are  most  common 
in  the  white  matter  of  the  centrum  ovale,  they  are  by  no  means 
unusual  in  the  brain-stem,  where  they  may  so  resemble  the 
normal  tissue  as  to  have  given  rise  to  the  old-fashioned  name 
of  "  hypertrophy  of  the  pons."  They  may  be  of  any  size  and 
shape,  and  their  limits  are  often  extremely  difficult  to  define. 
Owing  to  this  and  their  infiltrating  character,  gliomata  can 
very  rarely  be  removed  by  surgical  means.  Their  blood 
vessels  are  thin- walled  and  in  parts  very  scarce,  and  the  tumours 
are  therefore  liable  both  to  softening  and  to  haemorrhage  into 
their  substance.  Both  of  these  accidents  may  cause  destruction 
of  surrounding  nerve  cells  and  fibres,  and  thus  it  is  common  in 
the  clinical  history  of  such  a  case  for  focal  symptoms  to  appear 
suddenly  some  weeks  or  months  after  there  has  been  evidence  of 
cerebral  compression.  These  changes  are  characterised  macro- 
scopically  by  patches  of  a  reddish-brown  or  yellowish  hue, 
interspersed  among  the  greyish-red  and  more  opaque  white 
regions  distinctive  of  the  tumour  itself.  As  a  result  of  de- 
generative changes  cysts,  sometimes  of  large  size,  may  appear 
in  the  tumour.  The  growth  arises  usually  in  the  white  substance 
of  the  brain,  and  is  not  directly  connected  with  the  blood  vessels 
of  the  meninges,  but  it  may  reach  the  surface  and  form  a 
prominent  mass. 


GLIOMA 


241 


Fig.  69.  i 

Glioma  in  parieto-occipital  region  seen  on  the  mesial  surface  of  the 
left  hemisphere. 


Fig.  70. 

Glioma  of  corpus  c^llosum  with  numerous  haemorrhages. 


16 


242 


GLIOMA 


Microscopic  appearances. — As  pathological  neuroglia  cells 
are  of  very  various  forms,  so  it  is  natural  that  tumours  arising 
from  glial  tissue  should  be  characterised  by  the  variety  of  their 
histological  appearances.      Not  only  is  this  true  of  different 


Fig.  71. 

Cystic  glioma  of  left  frontal  lobe. 


tumours,  but  different  parts  of  the  same  tumour  often  present 
pictures  which  at  first  sight  have  no  resemblance  to  one  another. 
Thus,  one  part  may  be  a  mass  of  small  rounded  cells  with  com- 
paratively little  intercellular  network,  and  may  closely  resemble 


Fig.  72. 
Glioma  of  a  rather  fibrous  type 


Fig.  73. 
Diffuse  glioma  of  pons  {hypertrophy  of  pons) 


244 


GLIOMA  PONTIS 


Fig.  74. 
Diffuse  glioma  of  brain-stem  {sagittal  section) . 


Fig.  75. 
Glioma  of  pons  invading  fourth  ventricle. 


TUMOURS  OF  THE  BRAIN  245 

round-celled  or  mixed-celled  sarcomata ;  in  another  the  tumour 
may  consist  of  a  felted  mass  of  spider  cells,  while  in  yet  another 
part  cellular  elements  may  be  scanty,  some  small  and  rounded, 
others  giant  cells  resembling  multinucleated  amoeboid  glia 
cells.  Cells  with  polymorphous  or  ring-shaped  nuclei  are  not 
uncommon.  Round  cells  with  little  tendency  to  the  formation 
of  processes  are  common  in  all  forms  of  gliomata,  especially  in 
the  more  rapidly  growing  portions,  but  everywhere  the  variety 


Fig.  76. 

Glioma  pontis.     The  nerve  cells  in  the  infiltrated  area  are  undergoing 
degenerative  changes,  but  one  is  practically  normal. 

of  cells  met  with  is  a  most  striking  feature.  Some  tumours 
show  a  great  excess  of  the  large  forms  of  cells ;  others  tend  to 
approximate  to  the  appearances  of  sarcoma.  The  latter 
form  has  often  been  called  gliosarcoma,  but  as  this  term 
suggests  a  tumour  which  springs  partly  from  mesoblastic  and 
partly  from  epiblastic  (nervous)  elements,  it  is  apt  to  lead  to 
confusion.  Careful  examination  of  other  parts  of  the  tumour 
will  usually  resolve  all  doubts  as  to  the  category  in  which  the 
tumour  should  be  placed. 


246  NEUROBLASTOMA 

The  blood  vessels  are  usually  scanty.  Their  walls  are  thin 
and,  except  for  the  definite  lining  of  endothelial  cells,  which  is 
always  present,  supported  almost  entirely  by  glial  fibres. 
This  fact,  and  the  tendency  of  all  young  glial  tissue  to  de- 
generative changes,  make  haemorrhage  and  softening  common 
occurrences  in  gliomata. 

Ependymal  Glioma  (Neuro-epithelioma  Gliomatosum). 

This  is  a  form  of  tumour  which  is  most  commonly  met  with 
in  or  near  the  ventricles,  and  also  as  a  central  intramedullary 
tumour  of  the  cord.  It  usually  forms  a  circumscribed  mass  of 
more  or  less  rounded  character,  often  with  haemorrhages 
into  its  substance.  It  arises  from  cells  destined  to  form 
ependymal  cells,  and  presents  the  histological  appearances  of  an 
irregular  collection  of  tubules,  between  which  is  found  a  varying 
amount  of  gliomatous  tissue  similar  to  that  found  in  other 
gliomata.  Various  names  have  been  given  to  these  growths, 
which  are  by  no  means  common;  they  have  been  called  by 
Rosenthal  "  neuro-epithelioma  gliomatosum."  Similar  tubules 
of  cells  may  often  be  found  in  various  parts  of  true  gliomata. 
The  "  rosette  "  formations  of  retinal  gliomata  are  probably  of 
a  similar  nature. 

Neuroblastoma  (Ganglio-neuroma). 

These  tumours  may  occur  in  the  brain  as  fairly  well  defined, 
rounded  masses,  often  showing  some  haemorrhage  or  softening. 
While  they  are  more  easily  enucleated  from  the  brain  tissue 
than  the  gliomata,  they  do  not  come  away  clean,  but  separate 
through  a  zone  of  softening  or  gliosis  which  has  formed  around 
them.  Histologically  they  are  characterised  by  the  presence 
of  nerve  cells  and  fibres.  Some  of  the  cells  are  large  polygonal 
cells  with  clear  vesicular  nuclei  resembling  large  ganglion 
cells;  others  are  small  rounded  cells.  By  silver  staining 
methods  it  is  possible  to  make  out  numerous  nerve  fibres, 
which  can  be  traced  to  the  larger  cells.  The  blood  vessels 
are  usually  fairly  well  formed,  with  a  definite  endothelial 
lining  and  one  or  more  layers  of  fibrous  tissue. 


TUMOURS  OF  THE  BRAIN 


247 


Neuro-fibroma. 

The  incidence  of  neuro-fibromata  within  the  skull  is  chiefly 
on  the  acoustic  nerve.  Tumours  of  this  nature  arising  from 
the  eighth  nerve  are  commonly  found  in  the  cerebello-pontine 
angle,  and  give  rise  to  very  characteristic  clinical  symptoms. 
Usually  they  are  single,  but  they  may  be  bilateral,  in  which 
case  they  may  be  associated  either  with  generalised  neuro- 
fibromatosis, or  with  numerous  neuro-fibromata  of  the  cranial 


Fig.  77. 

Ganglip-neuroma.     High-power  view  of  ganglion  cell  area.     Note  amitotic 
division  of  nerve  cells.     (Bielschowsky's  stain.) 

and  spinal  nerve  roots.     In  a  few  such  cases  large  psammomata 
have  also  been  found  on  the  cortex  of  the  brain. 

Acoustic  nerve  tumours  are  irregularly  shaped,  rounded 
masses,  rarely  larger  than  a  hen's  egg,  covered  over  with  a  fibrous 
layer  derived  from  the  arachnoid.  On  section  they  are  firm 
and  fibrous,  and  may  show  smaller  or  larger  cysts  or  areas  of 
rarefaction.  Histologically  they  are  composed  of  elongated 
cells,  which  take  a  brownish  terra-cotta  colour  with  van 
Gieson's  stain,  quite  unlike  that  of  connective  tissue.     These 


248 


NEURO-FIBROMA 


cells  occur  in  bundles  and  whorls,  and  are  occasionally  seen 
lying  side  by  side,  nucleus  by  nucleus,  and  cytoplasm  by 
cytoplasm,  giving  a  banded  "  palisade  "  appearance  to  the 
field.  In  between  aggregations  of  such  cells  are  areas  of  a 
looser  reticular  appearance  suggesting  glial  or  myxomatous 
tissue.     These   appearances  account   for  the  terms   "  myxo- 


FiG.  78. 
N euro-fibroma  of  acoustic  nerve. 


fibroma  ''  and  "  fibro-glioma  "  having  been  used  to  describe 
these  tumours.  The  blood  vessels  are  formed  of  a  definite 
endothelial  lining  surrounded  with  one  or  more  layers  of  fibrous 
tissue  which  may  have  become  hyaline. 

Several  authors  have  considered  these  tumours  to  be  derived 
from  the  cells  of  the  sheath  of  Schwann,  and  the  term  "  neuri- 
noma "  has  been  used  with  this  meaning. 


TUMOURS  OF  THE  BRAIN 


249 


Carcinoma. 

Pure  carcinomata  of  the  brain  are  always  secondary  to 
tumours  in  other  organs,  especially  to  scirrhus  of  the  breast. 
Primary  intracranial  carcinomata  have  been  described,  but, 
with  the  exception  of  tumours  of  the  pituitary  gland,  these 
are  found  on  investigation  to  belong  either  to  the  form  of 
"  epithelioma  gliomatosum  "  described  above  (p.  246),  or  to  the 
endotheliomata.  Carcinoma-like  tumours  arising  from  the 
choroid  plexus  are  occasionally  found  in  relation  to  the 
ventricles. 


Fig.  79. 
Acoustic  nerve  tumour,  showing  "  palisade  "  arrangement  of  nuclei. 

Angeioma. 

This  form  of  growth  is  found  within  the  skull  either  as  a 
well-defined  mass  with  a  more  or  less  definite  capsule  or  more 
usually  as  a  diffuse  meningeal  naevus,  which  is  occasionally 
associated  with  a  similar  structure  involving  the  scalp. 
Angeiomata  are  also  described  in  connection  with  the  choroid 
plexus.  They  are  not  malignant  tumours,  but  may  give  rise 
to  severe  symptoms. 


250  TUMOURS  OF  THE  BRAIN 


Sarcoma. 

These  tumours  may  be  primary,  arising  from  the  cranial 
bones  or  the  meninges,  or  secondary,  when  they  may  be  found 
in  the  substance  of  the  brain.  They  are  very  variable  in  size 
and  in  rate  of  growth.  On  the  whole,  their  consistence  is  firmer 
than  that  of  the  gliomata,  and  sometimes  they  are  sufficiently 
well  defined  to  be  easily  removable  by  the  knife  of  the  surgeon, 
especially  when  the  growth  lies  on  the  surface  of  the  brain  and 


Fig.  8o. 
Carcinoma  in  the  cerebral  peduncles,  secondary  to  scirrhus  cancer  of  the  breast. 

has  not  penetrated  the  soft  meninges.  They  are  always  more 
clearly  defined  from  the  surrounding  brain  tissue  than  are  the 
gliomata. 

Diffuse  sarcomatosis  is  a  rare  condition  characterised  by  a 
general  invasion  of  the  meninges  of  the  brain,  and  sometimes 
those  of  the  spinal  cord  as  well,  by  sarcomatous  cells.  It  may 
be  primary  or  secondary  to  a  mass  of  growth  elsewhere. 

In  general  characters  the  sarcomata  within  the  skull  resemble 
those  found  in  other  parts.     The  majority  of  these  tumours 


TUMOURS  OF  THE  BRAIN 


251 


are  spindle-celled;  others  may  be  round-celled  or  mixed-celled. 
Sarcomata  arising  from  the  dura  mater  occasionally  erode  the 
cranial  bones  and  protrude  on  the  surface  of  the  skull. 

Perivascular  Sarcoma  (Perithelioma). 

These  tumours  may  grow  in  the  white  matter  of  the  brain 
without  any  obvious  meningeal  attachment.  They  are  slow- 
growing  tumours,  usually  single  and  showing  little  tendency 


Fig.  81. 
Perivascular  sarcoma.     High-power  view  of  small  vessel. 

to  form  metastases.  In  shape  they  are  irregularly  rounded, 
and  fairly  well  defined  from  the  surrounding  brain  tissue,  from 
which,  however,  they  do  not  peel  away  cleanly.  On  section 
they  are  rough  and  "  woolly,"  with  a  tendency  to  the  forma- 
tion of  cysts  or  small  areas  of  softening. 

Histologically  they  are  composed  of  masses  of  small  rounded 
or  stellate  cells  surrounding  a  central,  thick-walled  blood  vessel. 
In  some  of  the  slower  growing  forms  the  vessel  wall  shows  very 


252  SARCOMA 

great  hyaline  thickening,  which  may  exceed  the  width  of  the 
lumen.  In  the  more  rapidly  growing  forms  there  appears  to 
be  proliferation  of  the  smaller  vessels  to  form  several  channels 
which  run  together  in  a  "  leash  "  formation.  Their  walls 
show  considerable  fibrous  tissue  and  endothelial  proliferation, 
so  that  the  lumen  is  small  as  compared  with  the  thickness  of 
the  tissues  forming  its  wall.  At  a  definite  distance  away  from 
the  vessel  the  tumour  cells  tend  to  degenerate,  and  thus  in  the 
older  parts  of  the  growth  there  are  columns  of  cells  with  a 
central  blood  vessel  separated  from  one  another  by  necrotic 
cell  debris.  At  the  edge  of  the  tumour  these  cell  masses  are 
seen  to  invade  the  neighbouring  brain  substance  as  finger-like 
processes. 

It  has  been  suggested  that  these  tumours  arise  from  an  out- 
ward proliferation  of  the  cells  lining  the  adventitial  lymph 
spaces,  and  the  name  "  perithelioma  "  has  been  used  to  convey 
this  meaning,  but  as  this  theory  of  histogenesis  has  by  no 
means  met  with  universal  acceptance  it  is  better  to  retain  the 
older  name. 

Cylindroma  (Myxo-endothelioma). 

i  This  curious  form  of  tumour  occasionally  occurs  in  the 
brain,  usually  attached  to  the  meninges,  but  sometimes 
deeply  imbedded  in  the  brain  substance.  It  is  a  slow- 
growing  tumour,  which  occurs  in  children  more  often  than  in 
adults.  In  form  it  is  usually  an  irregularly  rounded,  bossed 
tumour  which  may  be  single  or  made  up  of  two  or  more 
masses,  easily  separated  from  one  lanother.  On  section  the 
appearance  is  that  of  a  sponge,  thin  strands  of  tissue  separating 
numerous  rounded  areas  of  all  sizes,  which  are  filled  with  a 
grey  gelatinous  substance. 

Histologically  they  present  a  very  definite  picture  of 
trabeculae  of  darkly  staining  epithelioid  or  fusiform  cells 
surrounding  areas  of  myxomatous  tissue.  The  trabeculae  are 
usually  covered  with  one  or  more  layers  of  cubical  cells  which 
have  a  considerable  resemblance  to  cubical  epithelium,  but 
towards  the  centre  of  the  trabeculae  the  cells  assume  a  more 
and  more  fusiform  type.  In  histological  appearances  these 
tumours  thus  resemble  to  a  certain  extent  the  endotheliomata, 
to  which  it  is  probable  that  they  are  allied.     They  are  also 


TUMOURS  OF  THE  BRAIN 


253 


closely  allied  to  the  "  mixed  tumours  "  of  the  parotid  and  other 
salivary  glands. 

Endothelioma. 

This  type  of  tumour  occurs  not  uncommonly  within  the 
cranium.  They  are  slow-growing  benign  tumours,  usually 
arising  from  the  arachnoid  or  the  dura  mater.  They  form 
rounded,  well-defined  masses  often  flattened  as  if  by  com- 
pression between  the  skull  and  the  brain.  Sometimes  they 
seem  to  grow  inwards  from    the  pia-arachnoid    as    globular 


w 


t*.'i 


^. 


Fig.  82. 
Cylindroma. 

tumours  attached  by  a  pedicle  to  the  meninges.  They  are 
usually  single,  but  may  be  multiple.  They  are  readily  removed 
by  surgical  intervention,  as  they  usually  push  the  pia  mater  in 
front  of  them.  Sometimes  they  grow  outwards,  infiltrating  the 
cranial  bones  and  producing  a  "  bossing  "on  the  surface  of  the 
skull.  The  bone  in  such  cases  may  be  over  an  inch  in  thickness, 
porous  and  soft.  It  is  common  to  find  slight  bony  thickening 
or  roughness  over  the  tumour,  and  this  may  be  visible  by  the 


254 


ENDOTHELIOMA 


Fig.  83. 
Etidothelioma  growing  from  falx  cerebri. 


tifiiltliC«l<(<l.l^ili1tlililili 


Fig.  84. 
Nodular  endothelioma  removed  by  operation. 


TUMOURS  OF  THE  BRAIN 


255 


X  rays.     A  common  site  of  origin  of  endotheliomata  is  the 
falx  cerebri  {)'dc  Fig.  8^). 

Histology. — They  are  composed  of  columns  or  whorls  of  cells 
which  resemble  endothelial  cells,  and  vary  in  shape  from  cubical 
epithelioid  cells  to  fine  fibrous  cells.  Usually  both  types  of  cell 
are  seen  in  the  tumour,  the  more  elongated  cells  forming  con- 
centric bands  which  surround  a  mass  of  more  cubical  cells.  All 
gradations  between   the  two  forms  are  present,  and  usually 


Fig.  85. 

Endothelioma  of  dura.   The  capsule  contains  a  large  vein.  The  tumour  is  formed 
of  larger  cells  incompletely  separated  from  one  another. 


there  is  no  difficulty  in  making  out  that  all  the  cells  are  essentially 
of  the  same  type.  Another  characteristic  feature  is  the  presence 
of  very  numerous  capillary  blood  channels  lying  either  between 
adjacent  columns  or  in  the  centre  of  whorls  with  no  wall  or 
lining  endothelium  other  than  the  cells  of  the  tumour.  There 
is  in  some  tumours  a  certain  amount  of  fibrous  tissue,  but  in 
others  this  is  quite  wanting  except  in  the  capsule,  which  is 
usually  formed  from  the  meninges. 


256  TUMOURS  OF  THE  BRAIN 

Psammoma. 

This  tumour  is  usually  an  indolent  endothelioma  undergoing 
calcareous  changes,  or  in  ether  instances  a  sarcoma  or  glioma 
in  which  are  numerous  concretions  of  mineral  matter. 

Cholesteatoma. 

This  curious  tumour,  of  which  the  origin  is  not  determined  with 
certainty,  may  be  single  or  multiple,  and  may  be  found"  either 
in  the  meninges  or  in  the  brain  substance.  It  has  a  shining, 
pearl-like,  pinkish-white  appearance,  and  is  usually  contained 
in  a  fibrous  capsule.  Histologically  it  consists  of  horny  cells 
resembling  those  of  the  skin  filled  with  cholesterin.  Hairs  and 
sebaceous  glands  are  occasionally  found  among  its  contents. 

Pituitary  Tumours. 

These  have  a  very  special  interest  from  their  associa- 
tion with  acromegaly  and  their  effects  on  the  functions 
of  the  pituitary  gland,  as  well  as  their  pressure  effects  on  the 
optic  chiasma  and  the  resulting  bi- temporal  hemianopsia. 
By  their  growth  they  expand  and  deepen  the  sella  turcica 
and  may  make  their  way  through  the  sphenoid  bone  into  the 
nasal  air  sinuses.  X-ray  examinations  of  the  floor  of  the  skull 
play,  therefore,  an  important  part  in  their  diagnosis.  Contrary 
to  the  general  rule  in  intracranial  neoplasm,  a  lymphocytosis 
in  the  cerebro-spinal  fluid  has  been  found  in  connection  with 
certain  tumours  in  this  region. 

Usually  pituitary  tumours  are  small,  rarely  exceeding  the  size 
of  a  walnut,  and  their  general  pressure  effects  are  of  less  clinical 
importance  than  those  due  to  local  pressure  and  to  alteration  of 
the  glandular  secretions.  Very  rarely,  even  in  malignant  forms, 
do  we  find  metastases  in  the  organs  of  the  body. 

In  acromegaly  the  commonest  change  found  in  the  gland  is 
simple  hyperplasia  or  adenomatous  formation  ("  chromophobe 
struma  "  of  Gushing) .  Hypertrophy  of  the  gland  with  increase 
of  the  colloid  material  has  been  described  as  occurring  after 
removal  of  the  thyroid  gland. 

Pituitary  cysts  may  be  found  in  the  pars  anterior  and  contain 
colloid  material,  or  may  arise  in  the  pars  nervosa  from  a  portion 
of  the  infundibular  canal.  Cholesterin-containing  cysts  are 
occasionally   found.     Dermoids   are   not   uncommon   in   this 


TUMOURS  OF  THE  BRAIN 


257 


region.     Other  less  benign  tumours  may  be  found,  as  endothe- 
liomata,  angeio-sarcomata,  primary  carcinomata  of  the  pars 


V 

Fig.  86. 
Pituitary  tumour. 

anterior,  and  sarcomata.  The  latter  are  usually  round-celled, 
but  spindle-celled  sarcomata  and  mixed-celled  sarcomata  with 
giant  cells  may  also  occur.        '  -" 

17 


258 


TUMOURS  OF  THE  BRAIN 


Pineal  Tumours. 

Tumours  of  the  pineal  are  usually  small,  of  the  size  of  a  hazel 
nut  or  less,  but  by  pressure  on  the  third  ventricle  and  iter  may 
cause  severe  symptoms.  They  are  usually  either  psammomata 
or  sarcomata.     Dermoid  tumours  have  also  been  described. 


Fig.  87. 
Dermoid  cyst. 


Dermoid  Cysts. 

These  cysts  are  rarely  found  within  the  skull,  but,  when  they 
occur,  show  a  preference  for  the  base  of  the  brain  and  resemble 
dermoid  cysts  in  other  parts. 


TUMOURS  OF  THE  BRAIN 
Parasitic  Cysts. 


259 


Hydatids  and  cysticerci  are  fairly  common  in  certain  countries 
and  are  more  often  single  than  multiple.  They  may  become 
calcified. 

Cysts  (Non-parasitic). 

In  this  group  may  be  included  traumatic  cysts,  develop- 
mental cysts,  and  certain  cysts  of  which  the  origin  is  unknown 
and  which  are  most  common  in  the  cerebellum.     It  must  be 


Fig.  88. 
Colloid  tumour  of  third  ventricle,  possibly  derived  from  the  pituitary. 

remembered  that  some  cyst-like  structures  are  really  gliomata 
which  have  degenerated,  and  that  their  gliomatous  nature  can 
only  be  recognised  by  careful  microscopical  examination. 
Meningeal  cysts  are  usually  inflammatory  in  origin,  and 
represent  the  results  of  some  previous  localised  meningitis  or 
meningo-encephalitis  (see  also  pseudo-porencephaly,  pp.  56 
and  121). 

Aneurysm. 

Aneurysmal  dilatations  of  the  cerebral  arteries  (p.  120)  give 
rise  to  symptoms  resembling  those  of  intracranial  tumours. 


26o  GENERAL  PATHOLOGY  OF 

General  Pathology  of  Intracranial  Tumours. 

Multiplicity. — The  gliomata  are  almost  invariably  solitary 
tumours,  and  the  same  may  be  said  of  the  endotheliomata, 
angeiomata,  cholesteatoma,  dermoid  cysts,  etc.  On  the  other 
hand,  sarcomata  and  carcinomata  are  not  infrequently  multiple. 

Rate  of  growth. — Most  gliomata  are  slow-growing  tumours, 
and  many  of  the  endotheliomata  show  the  same  character. 
The  sarcomata,  on  the  other  hand,  are  very  variable,  those 
arising  from  the  bone  or  dura  being  generally  less  rapid  in  their 
growth  than  those  found  in  connection  with  the  soft  meninges 
and  brain  substance.  Perivascular  sarcomata,  however,  are 
relatively  slow  growing  and  do  not  seem  to  cause  metastases. 
Considerable  increase  in  the  size  of  any  tumour  may  be  brought 
about  by  sudden  haemorrhages  into  its  substance,  and  this  is 
especially  frequent  in  the  gliomata. 

Effects  on  neighbouring  tissue. — A  growth  may  affect  the  brain 
tissue  in  which  it  originates  in  several  ways.  It  may  destroy 
the  nerve  elements,  or  it  may  modify  their  functional  activity 
profoundly  by  pressure.  Still  more  frequently  it  may  produce 
its  effect  by  interfering  with  the  circulation  through  the  neigh- 
bouring vessels,  and  so  bring  about  a  condition  of  oedema  which 
is  very  noticeable  in  the  vicinity  of  many  tumours  of  the  brain. 

Pressure  effects. — The  growth  of  a  tumour  within  the  skull, 
which  is  a  closed  cavity,  gives  rise  to  a  number  of  pressure 
effects  which  vary  in  degree,  to  a  certain  extent,  in  proportion 
to  the  rapidity  with  which  the  tumour  grows.  Flattening  of  the 
convolutions  is  the  most  obvious  result  on  opening  the  skull 
after  death  or  on  the  operating  table.  This  flattening  in  the 
case  of  the  cerebral  hemispheres  may  be  much  more  marked 
on  the  side  on  which  the  tumour  is  situated  than  on  the  opposite 
side,  and  it  is  often  attended  by  a  very' misleading  alteration 
in  the  cortical  geography.  For  instance,  the  Rolandic  fissure 
in  one  hemisphere  may  be  displaced  a  considerable  distance 
in  front  or  behind  the  corresponding  fissure  on  the  other  side. 
The  flattening  of  the  hemispheres  is,  however,  general  and 
equal  on  the  two  sides  in  the  case  of  tumours  below 
the  tentorium,  and  tumours  involving  the  corpora  quadri- 
gemina.  These  obstruct  the .  passage  of .  the  cerebro-spinal 
fluid  from  the  ventricles  and  give  rise. to  a. condition  of  hydro- 


TUMOURS  OF  THE  BRAIN 


261 


cephalus  which,  in  the  case  of  children,  may  burst  open 
the  cranial  sutures  and  cause  great  enlargement  of  the 
head. 

Localised   deformities   of   portions   of   the   brain   are    best 
exemplified  by  the  effects  of  tumours  in  the  cerebello-pontine 


Fig.  89. 
Hydrocephalus  produced  by  pontine  tumour. 

angle.  These  frequently  burrow  their  way  into  the  pons  and 
cerebellum  to  an  extent  which  is  quite  remarkable  when 
compared  with  the  relatively  slight  disturbance  of  function. 

Another  effect  of  the  general  increase  in  intracranial  pressure 
is  the  production  of  what  is  termed  a  pressure-cone  in  the 
posterior  fossa.     A  part  qf  the  cerebellar  hemisphere  on  each 


262  GENERAL  PATHOLOGY  OF 

side  is  forced  backwards  and  downwards  into  the  foramen 
magnum,  and  the  consequent  moulding  of  the  cerebellar  tissue 
is  readily  recognised  when  the  brain  is  removed  from  the  skull. 
In  connection  with  distension  of  the  ventricles,  it  must  be 
remembered  that  the  floor  of  the  third  ventricle  may  come  into 
contact  with  and  exert  pressure  on  the  optic  chiasma,  and  even 
on  the  pituitary  body  lying  in  the  sella  turcica.  This  has 
important  clinical  bearings,  owing  to  the  production  of  symp- 
toms pointing  to  hypopituitarism;  in  other  words,  to  a  syn- 


FiG.  90. 

A  pressure- cone. 

drome  which  we  are  in  the  habit  of  associating  with  inadequate 
activity  of  the  pituitary  gland. 

Osteo-porosis  or  thinning  of  the  cranial  bones  may  be  general 
in  the  case  of  long-standing  tumours  causing  increased  intra- 
cranial pressure,  or  may  be  localised  in  the  case  of  a  growth 
lying  between  the  brain  and  the  cranial  vault.  The  increase  of 
intracranial  pressure  frequently  interferes  with  the  function 
of  the  cranial  nerves  and  very  often  produces  changes  in  their 
structure.  The  sixth  pair  are  particularly  liable  to  suffer  in 
this  way,  partly  perhaps  by  reason  of  their  long  intracranial 
course  and  the  stretching  to  which  they  are  exposed,  partly 


TUMOURS  OF  THE  BRAIN  263 

owing  to  the  fact  that  they  are  subjected  to  the  full  pressure 
of  the  pons  above  them,  and  partly  in  some  cases  because  of 
their  intimate  relationship  to  the  branches  of  the  basilar  artery. 

Much  more  important  are  the  changes  in  the  optic  nerves 
which  follow  a  rise  of  intracranial  pressure,  and  to  which  is 
applied  the  term  optic  neuritis  or  papilloedema.  Much  con- 
troversy has  arisen  with  regard  to  the  actual  pathogenesis  of 
optic  neuritis.  Some  observers  consider  it  is  the  result  of 
direct  pressure  upon  the  optic  nerves,  while  others  suggest  a 
toxic  origin.  On  the  other  hand,  a  theory  has  been  propounded 
by  Paton  and  Holmes  that  the  venous  engorgement  and  lymph 
stasis  which  are  the  characteristic  anatomical  features  found 
in  the  heads  of  the  optic  nerves  are  brought  about  by  the 
increased  pressure  within  the  optic  nerve  sheath  and  its  in- 
fluence on  the  central  vein,  which  has  to  cross  that  sheath  in  its 
passage  from  the  nerve  through  the  orbit  to  the  cavernous 
sinus. 

The  results  of  increased  intracranial  pressure  are  not  confined 
entirely  to  the  structures  within  the  skull.  It  has  been  shown 
that  60  per  cent,  or  70  per  cent,  of  cases  of  intracranial  tumour 
are  associated  with  degenerative  changes  in  the  dorsal 
columns  and  dorsal  roots  of  the  spinal  cord,  and  it  is  sug- 
gested that  these  changes  are  brought  about  by  alteration  in 
the  pressure  of  the  cerebro-spinal  fluid  within  the  spinal  theca, 
and  possibly  by  stretching  of  the  dorsal  root  fibres  (Batten). 

Last  but  not  least  must  be  mentioned  the  effects  of  increased 
pressure  within  the  skull  on  those  vital  centres  in  the  medulla 
which  have  to  do  with  respiration  and  circulation;  effects 
which  are  the  direct  cause  of  the  fatal  result  when  surgical 
decompression  by  trephining  the  skull  has  not  been  carried  out. 

The  relationship  of  anatomical  to  clinical  phenomena. — The 
symptomatology  of  intracranial  tumours  may  be  divided 
into  two  parts,  focal  and  general.  The  focal  symptoms  are 
those  which  depend  upon  the  disturbance  of  function  produced 
by  the  tumour  in  its  immediate  neighbourhood,  and  will  vary 
according  to  the  site  of  the  growth.  They  are  very  numerous, 
and  may  be  psychical,  motor,  sensory  or  reflex.  The  general 
symptoms  are  those  which  are  dependent  upon  the  rise  of  intra- 
cranial pressure,  and  include  headache,  vomiting,  optic  neuritis, 
vertigo,  disturbancesof  circulation,  respiration  and  temperature, 


264  SPINAL 'TUMOURS 

as  well  as  abolition  of  tendon  jerks.  In  addition  to  these,  the 
rise  of  pressure  is  also  responsible  for  some  so-called  false 
localising  signs.  Such  is  the  paresis  of  an  external  rectus  muscle 
causing  diplopia,  which  is  brought  about  by  the  pressure 
exerted  on  a  sixth  nerve  in  the  way  already  referred  to. 

B. — Spinal  Tumours. 

The  classification  adopted  by  Bruns  is  a  convenient  one, 
and  it  may  be  used  here  for  our  purpose. 

1.  Tumours  which,  originating  in  its  envelopes,  secondarily 
affect  the  spinal  cord. 

{a)  Vertebral  tumours  arising  from  the  spinal  column  or 
the  soft  tissues  immediately  surrounding  it. 

{b)  Intravertebral  tumours,  which  may  be  divided  into 
two  classes  in  accordance  with  their  relation  to  the  dura 
mater. 

(i)  Extradural  tumours  arising  from  the  periosteum 
of  the  vertebrae,  the  outer  layers  of  the  dura  mater, 
or  the  fatty  alveolar  tissue  of  the  extradural  space. 

(2)  Intradural  tumours  growing  from  the  inner  layers 
of  the  dura  mater,  the  arachnoid,  the  ligamentum  den- 
ticulatum,  the  spinal  roots,  or  the  pia  mater. 

2.  Intramedullary  tumours  of  intrinsic  spinal  origin. 

I.  Tumours  of  the  Envelopes  of  the  Cord. 

{a)   Vertebral  Tumours. 

These  are  carcinomatous,  sarcomatous,  or  myelomatous  in 
nature.  Carcinoma  of  the  vertebral  column  is  always  secondary 
and  generally  metastatic,  although  occasionally  it  arises  by 
direct  extension  of  the  growth  from  other  organs.  The  primary 
focus  may  be  in  the  uterus,  stomach,  intestine,  prostate, thyroid, 
lung,  kidney  or  gall-bladder,  but  is  more  often  found  in  the 
mammary  gland  than  •  anywhere  else.  The  association  of 
carcinomata  of  the  spine  with  mammary  and  uterine  cancer 
accounts  for  the  fact  that  probably  75  per  cent,  of  cases  occur 
in  women. 

Morbid  anatomy. — It  is  almost  an  universal  rule  to  find  that 


TUMOURS  OF  THE  ENVELOPES  OF  THE  CORD     265 

the  spinal  column  is  much  more  extensively  involved  than  the 

symptoms  during  life  suggested,  and  it  is  by  no  means  un- 
common to  discover  that  the  replacement  of  bony  by  cancerous 
tissue  is  so  complete  that  the  spinal  cord  can  be  removed  from 
the  vertebral  canal  without  the  use  of  any  other  instrument 
than  a  knife.  The  growth  originates  in  the  spongy  portions  of 
the  bone,  destroying  the  medulla  and  filling  the  medullary 
spaces.  The  more  compact  bony  cortex  may  survive  as  a  thin 
shell  for  a  time,  but  ultimately  succumbs  to  the  expanding 
growth.  A  deposition  of  calcified  material  sometimes  goes 
along  with  absorption  of  bone,  and  exceptionally  leads  to  a  firm 
ankylosis  of  considerable  lengths  of  the  vertebral  column 
without  obvious  deformities.  More  commonly  the  softening 
produced  by  the  cancerous  infiltration  allows  the  body  weight 
to  bring  about  a  general  shortening  of  the  vertebral  column, 
or  in  other  cases  may  lead  to  local  collapse  and  the  formation 
of  angular  curvatures  resembling  those  of  spinal  caries.  Con- 
sidering the  extensive  neoplastic  formation,  the  amount  of 
superficial  change  in  the  appearance  of  the  vertebrae  is  extra- 
ordinarily small,  but  on  deep  examination  nodules  of  growth 
projecting  into  the  vertebral  canal,  and  sometimes  pressing  upon 
the  cord,  are  by  no  means  infrequent.  On  the  whole,  the  spinal 
roots  are  more  prone  to  suffer  than  the  spinal  cord,  as  they 
are  apt  to  be  involved  during  their  passage  through  the  inter- 
vertebral foramina. 

Sarcoma  may  be  primary  or  secondary  in  the  vertebral  column 
or  the  tissues  immediately  surrounding  it.  The  primary  form 
generally  commences  at  an  earlier  age  than  does  carcinoma, 
and  appears  to  have  a  special  predilection  for  the  lumbar  and 
sacral  regions.  The  secondary  sarcomata  either  extend 
directly  from  the  neighbouring  tissues,  from  the  organs  of  the 
thorax  or  abdomen,  or  represent  metastatic  deposits  from  more 
distant  parts,  especially  from  disease  in  other  bones.  The 
results  of  sarcomatous  infiltration  of  the  vertebral  column 
do  not  differ  essentially  from  those  produced  by  carcinoma, 
and  include  collapse,  angular  curvatures,  and  secondary  com- 
pression of  nerve  roots  or  of  the  spinal  cord  itself. 

Myeloma  occupies  an  intermediate  position  between  the 
malignant  and  benign  tumours  of  the  vertebrae,  both  as  regards 
its  course  and  its  histological  characters.     Multiple  myeloma- 


266  SPINAL  TUMOURS 

tosis  is  a  diffuse  infiltration  of  many  vertebrae,  causing  general 
softening  of  the  column  and  making  easy  the  production  of 
deformities  by  the  influence  of  weight  or  position.  Other  bones, 
especially  the  ribs,  sternum,  clavicle,  etc.,  are  frequently  in- 
volved at  the  same  time.  The  results  of  compression  resemble 
those  produced  by  carcinoma  or  sarcoma.  This  disease  is 
associated  with  the  presence  of  the  so-called  "  Bence- Jones  " 
albumoses  in  the  urine. 

The  benign  tumours  of  the  vertebral  column  are  rare.  They 
include  osteomata  and  exostoses,  myxomata,  chondromata, 
osteochondromata,  and  the  bony  excrescences  associated  with 
arthritis  deformans.  These  tumours  rarely  affect  the  nervous 
system,  but  occasionally  encroach  upon  the  neural  canal  or  the 
intervertebral  foramina  sufficiently  to  press  upon  the  spinal 
cord  or  spinal  roots. 

(b)  Intravertehral  Tumours. 

(i)  Extradural. — Tumours  in  this  space  are  generally  of 
secondary  origin,  and  are  more  often  sarcomatous  or  lipomatous 
than  any  other  variety.  It  is  a  favourite  site  for  the  forma- 
tion of  hydatid  cysts  when  they  produce  symptoms  of  spinal 
compression. 

(2)  Intradural. — In  this  situation  sarcoma  is  fairly  frequent 
and  is  seen  in  two  forms.  In  the  first  place,  there  may  be 
localised  growths  either  single  or  multiple  arising  in  con- 
nection with  the  inner  surface  of  the  dura  or  upon  the  spinal 
roots.  In  the  second  place,  there  may  be  a  diffuse  growth 
surrounding  and  enveloping  the  cord  over  very  considerable 
areas.  This  pial  sarcomatosis,  as  it  is  called,  is  usually  of  the 
round-celled  type,  and  has  been  regarded  as  a  secondary 
infection  from  some  primary  growth  situated  higher  up 
in  the  nervous  system  and  exposed  to  the  cerebro-spinal 
fluid. 

Neuro-fibromata  are  frequently  found  as  small  well-defined 
tumours  in  connection  with  the  spinal  roots.  They  are  often 
single,  but  may  be  multiple  and  may  be  associated  with  neuro- 
fibromatosis of  the  whole  peripheral  nervous  system.  We 
have  seen  several  cases  in  which  a  neuro-fibroma  has  grown 
out  through  the  intervertebral  foramen,  giving  rise  to  a  fairly 
large  encapsulated  tumour  which  lies  between  the  planes  of  the 


INTRAMEDULLARY  TUMOURS 


267 


spinal  muscles,  and  which  is  attached  by  a  thin  pedicle  to  a 
small  intradural  tumour. 

Endotheliomata  and  psammomata  are  also  common  growths 
in  this  situation.  Lipomata  and  lymphangiomata  are  more 
rarely  found.  Parasitic  cysts,  such  as  cysticerci  and  echinococci, 
have  also  been  observed. 

Intradural  tuniours  are  usually  situated  laterally  or  postero- 
laterally,  much  less  commonly  on  the  anterior  surface  of  the  cord. 


Fig.  91. 
Sarcoma  of  cord. 


2.  Intramedullary  Tumours. 

Growths  arising  within  the  cord  itself  are  more  common  in 
the  cervical  and  lumbo-sacral  enlargements  than  elsewhere, 
and  comprise  gliomata  and  ependymal  gliomata,  sarcomata, 
angio-sarcomata,  as  well  as  tuberculomata  and  gummata. 
Some  of  these  neoplasms  arise  in  reality  from  the  connective 
tissue  and  vascular  septa  which  penetrate  the  cord.  This 
is  usually  the  mode  of  origin  in  the  case  of  sarcomata  and  the 
granulomata.     The  latter  are  not  infrequently  multiple. 


268 


SPINAL  TUMOURS 


Fig.  92. 
Neuro-fibromatQSiis  of  cau4.a  equina, 


PATHOLOGY  OF  SPINAL  COMPRESSION        269 


3.  The  Pathology  of  Spinal  Compression. 

Tumours  of  the  meninges  produce  their  chief  effects  upon 
the  nerve  structures  within  the  vertebral  column,  and  rarely 
occasion  more  than  a  slight  erosion  of  the  bony  structures 
around.  The  spinal  roots,  although  to  some  extent  more 
resistant  than  the  spinal  cord,  are  often  the  first  to  suffer. 
They  may  be  directly  involved  in  the  growth  or  they  may 
be  compressed  either  in  their  intradural  or  their  inter- 
vertebral course.  In  either  case  degeneration  may  be  traced 
in  the  efferent  and  afferent  fibres. 

The  spinal  cord  itself  suffers  in  different  ways.  In  most 
cases  a  certain  amount  of  displacement  is  the  first  result,  and 
this  is  followed  by  compression.  The  early  effects  of  com- 
pression may  be  only  mechanical,  but  sooner  or  later  the 
circulation  of  the  compressed  region  is  interfered  with,  and 
oedema  and  anaemia  of  the  tissues  follow.  Oedema  is  prob- 
ably brought  about  by  venous  stasis,  and  has  an  important 
bearing  on  the  production  of  arterial  and  capillary  anaemia. 
In  some  cases  the  surface  arteries  may  also  be  compressed 
so  that  the  local  anaemia  is  exaggerated.  The  most  specialised 
nervous  structures,  particularly  the  large  ganglion  cells,  are 
the  first  to  show  signs  of  nutritional  disturbance,  and  the 
myelin  sheaths  of  the  tracts  in  the  white  columns  readily 
undergo  degeneration.  The  gradual  obliteration  of  the  circu- 
lation leads  to  areas  of  softening  which  may  be  associated  with 
neuroglial  proliferation  and  sclerosis  if  the  pressure  is  slowly 
exerted.  The  term  compression-myelitis,  which  indicates  an 
inflammatory  process,  is  hardly  justifiable.  In  some  cases 
softening  of  the  spinal  tissues  may  be  present  without  direct 
compression,  owing  to  the  interference  with  the  circulation  in 
the  superficial  arteries,  veins,  and  lymphatics.  Direct  in- 
filtration of  the  cord  by  extramedullary  tumours  is  less  fre^quent 
than  might  be  supposed,  the  pia-arachnoid  affording  a  certain 
amount  of  protection.  Occasionally  sarcomatous  cells  can  be 
traced  along  the  perivascular  lymphatic  channels  which 
accompany  the  radiating  vessels,  and  may  thus  gain  access  to 
the  central  parts. 

As  a  result  of  the  changes  just  described  at  the  level    of 


270    TUMOURS  OF  THE  BRAIN  AND  SPINAL  CORD 

compression,  secondary  degenerations  are  observed  in  the  long 
tracts  above  and  below,  and  similar  changes  are  also  seen  in  the 
ventral  spinal  roots. 


REFERENCES 

Adami,  J.  G. :  Principles  of  Pathology,  igio. 

Bruns,  L. :  Flatau,  Jacobson,  and  Minor,  Handbuch  der  Path.  Anat.  des  Nerven- 

systems,  1904,  Bd.  i.,  S.  515. 
Gushing,  H.:  Tumours  of  the  Nervus  Acusticus,  191 7. 
Durante,  G.  :  Nerfs  in  Manuel  d'Hist.  Path.,  Cornil  and  Ranvier,  vol.  iii., 

1907,  p.  425. 
GoMBAULT  AND  RiCHE :  Idem,  vol.  lii.,  1907,  p.  8;?. 
Greenfield,     J.     G.  :      "  Forty    Intracranial    Neoplasms,"     Brain,    191 9, 

vol.  xlii.,  part  i. 
Oppenheim:  Textbook  of  Nervous  Diseases.     Trans.  A.  Bruce,  1911. 
Ribbert:  Geschwulstlehre,  191 4. 
Verocay:  Zur  Kenntnis  der  "  Neurofibrome, "  Beitr.  z.  Path.  Anat.  u.  z.  allg. 

Path.,  1910,  Bd.  xlviii.,  S.  i. 


CHAPTER  IX 
DISEASES  OF  OBSCURE  ORIGIN 

I.  Motor  Neuron  Disease. 

The  above  title  indicates  conveniently,  if  not  very  correctly, 
the  whole  group  of  diseases  known  separately  under  the  names 
progressive  muscular  atrophy,  amyotrophic  lateral  sclerosis,  and 
btdbar  palsy.  These  cannot  be  differentiated  in  regard  to  the 
nature  of  their  pathology,  although  they  are  to  be  distinguished 
clinically  by  the  incidence  of  physical  signs  in  different  localities. 
For  instance,  "  progressive  muscular  atrophy  "  generally  refers 
to  a  clinical  condition  in  which  degeneration  of  the  spinal  lower 
motor  neurons  is  the  first  and  prominent  feature.  "  Bulbar 
palsy  "  embraces  similar  cases  in  which  the  lower  motor  neurons 
of  the  brain-stem  are  primarily  affected,  and  "  amyotrophic 
lateral  sclerosis  "  is  reserved  for  those  cases  in  which  de- 
generation of  the  upper  motor  neurons  is  at  least  as  conspicuous 
as  that  of  the  bulbar  or  spinal  lower  motor  neurons.  The 
inaccuracy  of  the  term  "  motor  neuron  disease  "  is  displayed  by 
the  anatomical  fact  that  the  degeneration  is  not  altogether 
limited  to  motor  tracts. 

Aetiology. — Little  is  known  about  the  cause  or  association 
of  this  disease.  Neither  clinical  nor  anatomical  data  favour 
the  view  that  the  disease  may  be  classed  among  the  abio- 
trophies, and  speaking  generally  it  has  no  hereditary  or  familial 
characteristics.  On  the  other  hand,  it  is  probable  that  such 
poisons  as  lead  and  syphilis  may  give  rise  to  conditions  which 
resemble  this  disease,  although  they  have  not  a  prominent 
place  in  its  causation.  It  may  be  assumed  as  probable  that 
other  toxic  agents,  either  endogenous  or  exogenous,  may  be 
responeible.  The  common  age  of  onset  is  after  the  completion 
of  the  third  decade  of  life,  but  so  many  cases  begin  between 
thirty  and  forty  that  it  is  hardly  justifiable  to  look  upon  the 
disease  as  in  any  way  an  indication  of  senile  decay.     Men 

271 


272  MOTOR  NEURON  DISEASE 

suffer  more  often  than  women,  and  the  cases  which  occur  in 
children,  although  somewhat  similar,  are  probably  of  a  different 
nature  as  far  as  their  origin  is  concerned. 

Pathogenesis. — It  is  generally  agreed  that  the  process  of 
degeneration  of  the  motor  neuron  is  a  primary  one  and  not 
secondary  to  changes  in  other  tissues,  and  it  is  also  clear  that 
the  affection  of  the  upper  motor  neuron  is  in  no  way  dependent 
on  that  of  the  lower  motor  neuron  and  vice  versa.  Very  rarely 
the  disease  has  appeared  in  persons  who  have  suffered  from 
acute  poliomyelitis  in  early  life,  but  the  frequency  of  this  com- 
bination is  not  sufficient  to  raise  it  above  the  level  of  a 
coincidence. 

Morbid  anatomy. — Macroscopical  changes  are  not  conspicuous. 
The  precentral  convolutions  of  the  brain  may  appear  to  be 
somewhat  atrophied,  and  the  bulk  of  the  grey  matter  in  the 
cervical  and  lumbo-sacral  enlargements  of  the  cord  may  appear 
to  be  diminished.  The  ventro-lateral  white  matter  may  appear 
shrunken  when  compared  to  the  dorsal  columns,  and  this 
contrast  is  emphasised  on  looking  at  a  Weigert-Pal  section  of 
the  spinal  cord,  in  which  the  dark  colour  of  the  dorsal 
columns  is  brought  into  relief  by  the  comparative  pallor  of  the 
rest  of  the  white  matter.  Finally,  there  is  a  difference  between 
the  ventral  and  dorsal  root  fibres,  the  former  being  less  opaque 
and  more  reddish-grey  than  the  latter. 

Examination  of  a  Weigert-Pal  section  of  the  spinal  cord 
under  a  low  power  reveals  a  pallor  of  the  ventro-lateral  white 
matter  which  is  not  equal  in  degree  all  over,  but  is  especially 
well  marked  in  the  pyramidal  tracts.  There  is  a  conspicuous 
absence  of  myelinated  fibres  in  the  ventral  grey  matter  and 
in  the  position  of  the  intramedullary  portions  of  the  ventral 
roots.  On  the  other  hand,  the  dorsal  root  fibres  can  be 
easily  seen.  A  Marchi  preparation  exhibits  a  preponderance 
of  degeneration  in  the  same  regions,  and  the  fibres  of  the 
ventral  commissure  are  also  shown  to  be  affected.  The  amount 
of  degeneration  seen  by  this  method  varies  in  different  cases 
according  to  the  length  of  the  course  of  the  disease;  the  more 
acute  cases  display  the  greater  number  of  blackened  myelin 
sheaths. 

Sections  stained  by  the  Nissl  or  haematoxylin  method  show 
the  characteristic  changes  in  the  ventral  horns.     The  ganglion 


MOTOR  NEURON  DISEASE 


273 


cells  are  decreased  in  number,  and  of  those  which  remain  only 
a  few  present  a  healthy  appearance.  The  majority  exhibit  dif- 
ferent stages  of  atrophy.  They  are  smaller  than  normal,  some 
are  rounded  or  oval,  and  others  more  angular  in  shape.  The 
usual  granulation  has  disappeared,  or  is  less  conspicuous,  and 
the  amount  of  pigment  is  often  increased.  The  latter  appears 
to  displace  the  shrunken  nucleus  into  a  corner  of  the  cell  in 
some  instances.  It  is  especially  noticeable  that  chromatolytic 
changes  are  hardly  ever  observed  except  in  cases  which  have 
run  a  very  acute  course. 


Fig.  93. 

Amyotrophic  lateral  sclerosis.  Section  from  the  cervical  enlargement  show- 
ing the  degeneration  in  the  antero-lateral  column  and  especially  in  the  pyra- 
midal tracts.  Dorsal  roots,  dorsal  columns  and  direct  cerebellar  tracts  are 
normal. 


Changes  in  the  ground  substance  are  relatively  slight,  but 
some  compensatory  neuroglial  proliferation  is  to  be  seen,  and 
occasionally  small  vessels  show  some  dilatation  and  perhaps  a 
slight  cellular  infiltration  of  their  walls. 

The  changes  in  the  spinal  cord  described  above  are  also  to 
be  found  in  the  grey  matter  of  the  bulb  in  connection  with 
certain  nuclei  in  the  so-called  bulbar  cases.  The  nuclei  of  the 
spinal  accessory  and  hypoglossal  nerves,  the  nucleus  ambiguus 
and  the  motor  nucleus  of  the  fifth  nerve,  are  most  com- 
monly affected,  but  occasionally  changes  of  a  similar  character 

•  18 


274  MOTOR  NEURON  DISEASE 

are  seen  in  the  facial  nucleus  and  in  parts  of  the  nuclei  of  the 
sixth  and  third  nerves. 

Atrophic  changes  resembling  those  seen  in  the  spinal  and 
bulbar  cells  are  observed  in  the  Betz  cells  of  the  precentral 
convolutions,  and  here  again  the  number  of  cells  may  be 
conspicuously  small.  The  degeneration  in  the  long  tracts, 
especially  the  pyramidal,  may  be  traced  by  the  Marchi  method 
through  the  brain-stem  and  the  internal  capsule  as  far  as  the 
cortex.  By  the  same  method  degenerated  fibres  can  be  seen 
in  the  posterior  longitudinal  bundles,  in  Monakow's  bundle, 
and  occasionally  in  the  fillet.  The  middle  portion  of  the  corpus 
callosum  is  frequently  affected  in  the  same  way,  the  fibres  in 
this  situation  being  probably  collaterals  of  the  pyramidal 
tract. 

Although  the  pyramidal  fibres  are  affected  as  a  whole,  the 
degeneration  appears  to  be  older  and  more  complete  in  those 
parts  of  the  fibres  which  are  most  distant  from  the  Betz  cells — 
that  is  to  say,  near  their  termination  in  various  levels  of  the 
spinal  cord.  The  degenerative  changes  in  the  vential  roots 
and  in  the  peripheral  nerves  are  often  difficult  to  detect,  a  fact 
which  is  only  reconcilable  with  the  view  that  the  products  of 
degeneration  are  rapidly  removed  in  those  structures,  and  that 
the  disappearance  of  fibres  is  not  easy  to  demonstrate  unless 
those  products  can  be  found.  In  the  more  acute  cases  the 
Marchi  method  displays  the  degeneration  which  one  would 
naturally  expect. 

The  changes  in  the  affected  muscles  are  of  an  atrophic 
character,  and  they  are  characterised  by  the  fact  that  different 
bundles  show  different  degrees  of  shrinkage.  The  muscles  are 
flabby  and  pale  in  appearance,  and  microscopical  sections  show 
that  the  fibres  are  diminished  in  calibre,  although  retaining  a 
certain  amount  of  transverse  striation.  Some  bundles  show  a 
complete  absence  of  muscular  tissue,  the  fibres  having  been 
replaced  by  clumps  of  sarcolemma  nuclei  which  undergo  pro- 
liferation during  the  process  of  atrophy.  Occasional  swollen 
fibres  are  seen,  and  these  may  present  other  degenerative 
changes  in  the  shape  of  fissures  and  vacuolation.  While 
there  is  a  considerable  increase  of  fibrous  tissue,  it  is  noticeable 
that  an  excess  of  fat,  such  as  is  seen  in  the  myopathic  diseases, 
is  never  laid  down. 


AMYOTROPHIC  LATERAL  SCLEROSIS  275 


Fig.  94. 

Muscles  in  amyotrophic  lateral  sclerosis,     a.  Early  degeneration  of  muscles. 
b,  Advanced  atrophy  of  muscle,  the  muscle  spindles  escaping. 


276 


MOTOR  NEURON  DISEASE 


The  relation  of  the  anatomical  to  the  clinical  phenomena. — In 
progressive  muscular  atrophy  and  bulbar  palsy  the  atrophy 
of  certain  muscles  is  the  conspicuous  clinical  feature,  and  it  is 
generally  observed  that  the  affected  muscles  show  loss  of  power 
in  proportion  to  their  wasting.  While  some  bundles  may  have 
disappeared,  others  contract  to  the  best  of  their  ability,  in 
response  both  to  the  will  and  to  electrical  stimuh,  until  such 
time  as  they,  too,  have  dwindled  into  insignificance      For  this 


Fig.  95. 
Amyotrophic  lateral  sclerosis.     Longitudinal  section  of  atrophied  muscle  fibre. 


reason  it  is  unusual  to  find  the  true  reaction  of  degeneration, 
such  as  is  met  with  in  acute  poliomyelitis  or  in  various  forms 
of  peripheral  neuritis.  Similarly,  the  tendon  jerk  may  be 
elicited  in  relation  to  muscles  which  are  considerably  atrophied, 
and  the  readiness  of  the  response  may  be  attributed  to  the 
degeneration  which  is  going  on  simultaneously  in  the  upper 
motor  neurons.  For  some  reason  which  is  still  obscure  the 
lateral  sclerosis,  so  easily  demonstrated  clinically  by  the 
exaggeration  of  the  deep  reflexes,  is  not  always  associated  with 


SUBACUTE  COMBINED  DEGENERATION       277 

the  extensor  type  of  plantar  reflex.  Finally,  it  should  be  noted 
that  in  cases  in  which  the  clinical  symptoms  have  pointed  to 
degeneration  of  the  lower  motor  neurons  only,  it  is  an  almost 
invariable  rule  to  find  after  death  that  changes  have  also  taken 
place  in  the  pyramidal  and  other  long  tracts  of  the  spinal  cord. 

2.  Subacute  Combined  Degeneration  of  the  Spinal  Cord. 

This  very  definite  disease  has  only  received  its  proper  share 
of  recognition  during  the  present  century,  and  though  its 
clinical  features  are  sufliciently  characteristic  for  the  purposes 
of  diagnosis,  there  is  still  considerable  obscurity  about  the 
cause  and  actual  nature  of  the  pathological  process. 

Aetiology. — It  is  a  disease  of  advanced  middle-age,  the 
majority  of  cases  beginning  between  fifty  and  sixty.  It  has 
been  known  to  occur  soon  after  thirty  and  as  late  as  sixty-five. 
Both  sexes  are  about  equally  affected,  and  heredity  or  familial 
influences  do  not  appear  to  play  any  part.  It  has  no  definite 
associations  with  any  other  disease,  although,  it  has  sometimas 
been  observed  in  persons  who  have  suffered  from  syphilis  and 
from  chronic  suppuration.  On  the  other  hand,  a  history  of 
gastro-intestinal  disturbances,  in  one  case  a  prolonged  colitis,  is 
not  uncommon  in  connection  with  the  early  symptoms  of  the 
disease  or  with  the  period  which  immediately  precedes  the 
development  of  any  nervous  phenomena.  Without  any 
suflicient  proof,  there  is  a  general  tendency  to  associate  the 
disease  with  septic  conditions  of  the  gastro-intestinal  tract. 

Pathogenesis. — -The  fact  that  the  nervous  troubles  are  often 
accompanied  by  a  severe  form  of  anaemia,  and  the  fact  that  in 
cases  of  pernicious  anaemia  without  nervous  symptoms  some 
spinal  changes  are  occasionally  observed,  have  led  some 
observers  to  regard  the  anaemia  as  a  primary  feature  in  the 
production  of  this  spinal  disease.  This  view  cannot  be  sup- 
ported, because  the  experience  of  the  last  ten  years  has  shown 
more  and  more  conclusively  that  the  spinal  condition  may  run 
its  course  without  the  occurrence  of  any  changes  in  the  blood 
at  any  stage.  The  view  that  the  spinal  changes  and  the 
anaemia,  when  it  occurs,  are  both  secondary  to  some  toxic 
influence  is  now  generally  accepted.  With  regard  to  the 
nature  of  the  morbid  changes  in  the  central  nervous  system 
there  is  no  such  general  agreement.     Some  authors  think  that 


278        SUBACUTE  COMBINED  DEGENERATION 

the  essential  lesions  are  necrotic  foci  making  their  appearance 
i  1  the  posterior  and  lateral  columns,  spreading  centrifugally, 
and  bringing  about  secondary  degeneration  of  the  long  descend- 
ing and  ascending  tracts.  This  view  assumes  that  focal 
lesions  are  primary,  and  systemic  degenerations  are  purely 
secondary  phenomena.  Other  observers  prefer  to  regard  the 
system  degeneration,  which  undoubtedly  occurs,  as  being  to  a 
great  extent  independent  of  the  focal  lesions,  although  the 
latter  must  necessarily  play  their  part  in  affecting  the  fibres 
of  the  long  tracts.  The  fact  that  there  is,  speaking  generally, 
an  extraordinary  symmetry  in  the  lesions  of  this  disease  favours 
the  theory  that  systematic  degeneration  is  not  altogether 
dependent  upon  the  incidence  of  necrotic  foci,  which  would 
be  very  unlikely  to  fall  so  symmetrically  upon  each  lateral 
half  of  the  spinal  cord. 

There  is  no  adequate  support  to  be  obtained  from  micro- 
Gcopical  investigation  for  the  theory  that  the  morbid  process  is 
an  inflammatory  one,  and  there  is  an  equal  lack  of  evidence 
in  favour  of  the  view  that  the  focal  necroses  are  the  result  of 
vascular  lesions.  It  is  true  that  in  those  parts  of  the  cord 
which  are  most  severely  affected,  the  vessel  walls  may  show 
fatty  and  other  degenerative  changes,  but  the  examination  of 
a  large  number  of  cases  shows  that  vascular  changes  are  by  no 
means  general,  and  may  frequently  be  absent  in  those  parts 
where  parenchymatous  changes  are  more  or  less  recent. 
Although  the  areas  of  degeneration  have  no  particular  relation 
to  vascular  supply,  yet  it  is  worthy  of  note  that  the  maximum 
change  is  to  be  found  in  the  mid-thoracic  region — that  is  to  say, 
at  the  level  where  the  blood  supply  to  the  spinal  cord  is  least 
rich.  Finally,  there  is  another  feature  of  the  pathological 
process  which  deserves  attention,  although  its  significance  is 
obscure;  we  refer  to  the  fact  that  there  is  singularly  little 
neuroglial  reaction  in  this  disease  as  compared  to  that  which 
occurs  in  most  other  morbid  conditions,  degenerative  or  in- 
flammatory, of  the  spinal  cord. 

It  is  probable  both  from  clinical  and  pathological  findings 
that  the  longest  fibres  of  the  cord  usually  suffer  first.  This 
can  be  readily  understood  on  the  supposition  that  the  disease 
is  due  to  toxins  circulating  in  the  blood  stream.  The  longest 
fibres  in  the  cord,  as  in  the  peripheral  nerves,  are  the  most 


SUBACUTE  COMBINED  DEGENERATION        279 


Fig.  96. 

Subacute  combined  degeneration  of  cord.  Three  sections  representing  the 
changes  seen  in  the  cervical,  thoracic  and  lumbar  regions  stained  by  the 
Weigert-Pal  method. 


28o        SUBACUTE  COMBINED  DEGENERATION 

vulnerable,  especially  in  the  mid-thoracic  region,  where  their 
blood  supply  is  poorest. 

Morbid  anatomy. — Gross  changes  are  generally  conspicuous 
by  their  absence.  The  cerebral  hemispheres  may  appear  some- 
what shrunken  in  long-standing  cases,  especially  in  the  fronto- 
parietal region.  Some  compensating  excess  of  fluid  in  the 
meninges  may  be  present  over  the  atrophied  convolutions.  The 
cord  is  little  altered  in  size  or  shape,  but  it  may  display  a 
surface  which  is  less  opaque-looking  than  normal.  On  trans- 
verse section  the  degeneration  of  the  white  columns  is  con- 
spicuous by  reason  of  their  greyish  translucent  appearance. 
The  grey  matter,  the  meninges  and  the  spinal  roots  are  not 
altered. 

The  characteristic  changes  in  the  cord  are  best  illustrated 
by  a  series  of  sections  from  different  levels  stained  by  the 
Weigert-Pal  method.  These  preparations  show  that  the 
pathological  process  is  confined  to  the  white  matter,  and  that 
the  latter  is  more  profoundly  affected  in  the  mid-thoracic  region 
than  at  the  extremities  of  the  ccrd.  The  amount  of  degenera- 
tion varies  with  the  duration  of  the  disease  in  different  cases, 
but  it  is  by  no  means  uncommon  to  find  the  whole  of  the  white 
matter  in  the  thoracic  region,  with  the  exception  of  the  short 
internuncial  fibres  surrounding  the  grey  matter,  devoid  of 
myelin.  In  the  higher  cervical  region  the  ascending  tracts,  and 
in  the  lower  lumbo-sacral  region  the  descending  tracts,  are 
most  severely  affected.  In  addition  to  the  uniform  degenera- 
tion of  these  long  tracts  necrotic  foci  may  be  found  scattered 
here  and  there  in  such  a  way  as  to  suggest  that  by  their  ex- 
tension and  fusion  they  may  have  contributed  directly  and 
indirectly  to  the  general  destruction  of  conducting  fibres.  The 
degeneration  is  more  or  less  symmetrical,  but  the  necrotic 
foci  do  not  always  conform  to  this  symmetry,  and  may  be 
present  in  parts  which  are  otherwise  normal  on  one  or  other 
side  of  the  cord. 

Marchi-stained  preparations  enable  the  observer  to  differ- 
entiate between  the  older  and  the  more  recent  patches  of  disease, 
although  there  is  often  a  poor  line  of  demarcation.  Recently 
degenerated  fibres  stand  out  as  rounded  black  dots,  while 
regions  which  have  been  longer  affected  only  contain  masses  of 
altered  myelin  in  the  perivascular  lymphatics. 


^^^^^^^3^S^ 


Fig.  97. 

Two  transverse  sections  and  one  longitudinal  section  from,  a  case  of  subacute 
combined  degeneration,  stained  by  the  Marchi  method. 


282        SUBACUTE  COMBINED  DEGENERATION 

Under  higher  powers  the  tissue  of  the  white  matter  has,  in 
many  places,  a  vacuolated  appearance  due  to  the  fact  that 
both  myelin  sheaths  and  axis  cylinders  have  disappeared, 
leaving  numerous  spaces  divided  from  each  other  by  delicate 
strands  of  neuroglial  tissue.  Amylaceous  bodies  are  some- 
times seen  in  considerable  numbers.  Dilatation  of  lymph 
spaces  and  oedema  of  the  nerve  roots  are  commonly  seen. 

The  blood  vessels  may  be  thickened  and  hyaline ;  on  the  other 
hand,  vascular  changes  may  be  conspicuously  absent.  Capil- 
lary haemorrhages  are  sometimes  observed.  Evidence  of 
inflammatory  reaction  in  the  way  of  cellular  proliferation  is 
extremely  scanty  or  altogether  wanting. 

The  ganglion  cells  of  the  \entral  grey  matter  are  usually 
healthy,  but  those  of  Clarke's  column  may  show  chromolytic 
changes.  These  cell  changes  are  probably  secondary  to  the 
degeneration  of  the  direct  cerebellar  tracts,  and  analogous 
alterations  are  to  be  found  in  the  Betz  cells  of  the  cerebral 
motor  cortex  secondary  to  the  destruction  of  pyramidal  fibres 
in  the  cord. 

The  spinal  roots  and  peripheral  nerves  are  healthy,  but 
muscles  which  have  been  long  paralysed  are  often  small  in  bulk 
and  contain  fibres  which  are  decreased  in  diameter  and  poorly 
striated. 

The  blood  may  be  up  to  the  normal  standard  or  may  show 
signs  of  an  anaemia  of  varying  degrees  of  severity.  The  colour- 
index  is  generally  high.  Normoblasts  and  megaloblasts  may  be 
present,  and  poikilocytosis  is  commonly  observed.  A  relative 
lymphocytosis  of  over  30  per  cent,  is  common.  Sometimes 
the  changes  in  the  nervous  system  are  associated  with 
lymphatic  leukaemia,  pernicious  anaemia,  or  the  cachexia  of 
malignant  disease.  In  other  organs  changes  are  not  constant, 
but  ulceration  and  inflammatory  lesions  of  the  alimentary 
canal  are  by  no  means  uncommon.  The  kidneys  may  be  the 
seat  of  septic  processes  secondary  to  cystitis,  if  the  bladder 
has  been  infected. 

Relationship  of  anatomical  to  clinical  phenomena. — In  the 
early  stages  of  subacute  combined  degeneration  the  chief 
clinical  feature  is  a  slight  degree  of  paraplegia,  which  may  be 
ataxic  or  spastic  or  a  mixture  of  both.  This  depends  on  the 
affection  of  the  posterior  columns  and  the  pyramidal  tracts. 


DISSEMINATED  SCLEROSIS  283 

In  some  cases  in  which  ataxy  with  diminished  tendon  jerks 
and  perhaps  Hghtning  pains  are  the  chief  early  symptoms 
the  chief  incidence  of  the  disease  is  in  the  posterior  columns. 
In  others  a  spastic  paraplegia  with  increased  tendon  jerks  and 
extensor  plantar  responses  denotes  early  involvement  of  the 
pyramidal  tracts.  The  third  stage  of  the  disease  is  often 
ushered  in  by  a  flaccid  paraplegia  with  complete  sensory  loss 
up  to  a  certain  level,  with  absent  tendon  jerks  and  paralysed 
sphincters.  This  symptom-complex  can  be  explained  by  the 
complete  loss  of  function  on  the  part  of  all  the  long  tracts  of 
the  spinal  cord  in  the  dorsal  region,  an  event  which  is  easily 
understood  when  the  segments  of  that  level  are  examined  post 
mortem.  In  the  authors'  experience  cases  with  preponderating 
involvement  of  the  posterior  columns  run  a  shorter  course  than 
those  in  which  the  lateral  columns  are  more  affected. 

3.  Disseminated  Sclerosis. 

Disseminated  sclerosis  is  a  common  disease  of  the  nervous 
system;  but  although  a  great  deal  is  known  with  regard  to 
its  anatomical  and  clinical  features,  its  true  nature  is  by  no 
means  fully  understood.  As  far  as  its  pathological  anatomy 
is  concerned,  it  may  be  said  to  stand  alone  and  to  have  little 
in  common  with  other  diseases  of  the  nervous  system,  and 
particularly  slight  relationship  to  other  conditions  going  by 
the  name  of  sclerosis. 

Aetiology. — The  onset  of  symptoms  occurs  as  a  rule  in  the 
second,  third,  or  fourth  decade  of  life,  although  there  are 
records  of  doubtful  cases  beginning  somewhat  earlier,  and  we 
have  met  with  a  case  commencing  at  about  the  age  of  fifty, 
which  was  verified  by  autopsy.  The  two  sexes  are  about 
equally  affected,  and  there  is  nothing  beyond  the  very  oc- 
casional occurrence  of  the  disease  in  two  members  of  the  same 
family  to  suggest  that  it  has  any  hereditary  or  familial  origin. 
It  is  not  an  uncommon  thing  for  the  symptoms  of  disseminated 
sclerosis  to  make  their  first  appearance  in  the  sequel  of  some 
acute  infective  fever,  but  it  has  been  impossible,  so  far,  to 
trace  any  accurate  relationship  with  any  one  of  them.  On  the 
other  hand,  it  is  an  undoubted  fact  that  syphilis  plays  no 
part  in  its  causation.  As  in  the  case  of  most  diseases,  trauma, 
shock,  worry,  overwork,  and  chills  have  all  been  regarded  at 


284  DISSEMINATED  SCLEROSIS 

some  time  or  by  some  observers  as  important  factors,  but  no 
evidence  more  valuable  than  that  which  depends  on  post  hoc 
data  for  its  credibility  has  been  produced  in  support  of  these 
charges.  For  some  years  opinion  has  gradually  come  round 
to  the  view  that  some  toxic  agent,  possibly  some  specific 
organism,  is  responsible.  The  course  of  the  disease  is  generally 
paroxysmal  with  longer  or  shorter  remissions  over  a  great 
number  of  years,  and  in  this  shows  some  resemblances  to 
cerebro-spinal  syphilitic  affections.  It  therefore  seems  likely 
that  the  virus  of  disseminated  sclerosis  is  stored  up  in  the 
human  body  in  a  way  resembling  that  in  which  the  virus  of 
syphilis  is  retained.  If  this  is  the  case,  the  raids  on  the 
nervous  system  which  take  place  from  time  to  time  may  be 
connected  with  some  of  the  factors  mentioned  above  as  being 
of  aetiological  importance.  Mott  has  suggested  that  the 
pathology  of  the  disease  may  be  explained  by  the  action  of 
some  lipolytic  ferment  upon  the  medullary  sheaths  of  the 
central  nervous  system. 

Within  the  last  few  years  various  observers  both  in  this 
country  and  on  the  Continent  have  obtained  results  which 
appear  to  show  that  disseminated  sclerosis  is  due  to  the  action 
of  a  spirochaete.  The  cerebro-spinal  fluid  or  the  blood  of 
patients  suffering  from  the  disease  when  injected  into  rabbits 
and  guinea-pigs  produced,  after  an  incubation  period  varying 
from  three  days  to  twelve  weeks,  symptoms  of  paralysis  often 
ending  in  death.  In  some  cases  material  from  an  infected 
animal  has  given  rise  to  the  disease  in  a  second,  and  passage 
has  been  continued  up  to  a  fourth  guinea-pig  without  alteration 
of  virulence.  In  these  animals  spirochaetes  were  found  in  the 
blood,  both  before  and  after  death,  in  the  liver,  and  by 
Marinesco'in  the  cerebro-spinal  fluid  drawn  from  the  fourth 
ventricle.  Siemerling  found  living  spirochaetes  two  hours 
after  the  death  of  a  patient  in  early  patches  of  disseminated 
sclerosis  by  using  the  dark-ground  illumination  method,  but 
he  was  unable  to  find  them  in  stained  specimens.  These 
observations  require  confirmation,  both  from  the  side  of  histo- 
pathology  and  by  the  demonstration  of  spirochaetes  in  the 
human  subject. 

Pathogenesis. — As  might  be  expected  in  a  disease  which  is 
characterised  partly  by  a  destructive  process  of  nerve  elements 


DISSEMINATED  SCLEROSIS  285 

and  partly  by  an  overgrowth  of  neuroglial  tissue,  different 
views  have  been  held  as  to  which  process  is  primary  and  which 
is  secondary.  The  prevailing  opinion  among  those  who  are  best 
qualified  to  judge  is  in  favour  of  a  primary  affection  of  the 
nerve  tissues  and  a  secondary  hyperplasia  of  the  neuroglia, 
which  is  regarded  as  a  process  of  repa'  ation.  In  answer  to 
those  who  regard  disseminated  sclerosis  as  merely  a  chronic 
form  of  myelitis  may  be  put  forward  the  fact  that  we  are  not 
acquainted  with  any  form  of  chronic  inflammation  in  the 
central  nervous  system  which  produces  results  at  all  comparable 
from  a  histological  point  of  view  with  those  of  the  disease  under 
discussion.  Attempts  which  have  been  made  to  correlate  the 
patches  of  sclerosis  with  vascular  changes  have  proved  abortive 
in  view  of  the  fact  that  in  many  cases  no  disease  of  the 
blood  vessels  can  be  detected. 

We  are  forced  to  the  conclusion,  therefore,  that  whatever  be 
the  nature  of  the  agent  at  work,  its  effect  falls  primarily  on  the 
medullary  sheaths  of  the  central  nervous  system,  and  that 
other  processes,  such  as  neuroglial  proliferation,  meningeal 
thickening,  and  axonal  degeneration,  are  entirely  secondary. 

Morbid  anatomy. — From  the  anatomical  standpoint,  dis- 
seminated sclerosis  is  a  disease  of  the  whole  cerebro-spinal  axis, 
and  is  rarely  if  ever  limited  either  to  the  brain  or  to  the  spinal 
cord.  The  characteristic  patches  of  the  disease  are  scattered 
in  haphazard  fashion  over  the  whole  of  the  central  nervous 
system,  and  are  sometimes  found  as  well  in  some  of  the  cranial 
nerves.  The  patches  present  litt'c  uniformity  of  shape  or  size. 
Their  outline  is  always  irregular,  and  they  vary  from  a  few 
millimetres  in  diameter  to  the  dimensions  of  a  walnut.  In 
examining  a  recent  brain  and  spinal  cord,  the  patches  are 
easily  detected  both  by  the  eye  and  hand.  They  present  a  less 
opaque  and  more  translucent  appearance  than  that  of  the 
surrounding  parts ;  their  consistence  is  often  gelatinous  and  their 
colour  a  dull  grey  or  greyish-red.  Passing  the  fingers  along  the 
spinal  cord,  a  curious  uneven  knobbly  sensation  is  experienced, 
which  is  unlike  that  observed  in  any  other  disease.  The  patches 
are  found  both  on  and  away  from  the  surface,  and  they  cannot 
be  said  to  show  any  decided  preference  for  either  the  grey  or 
the  white  matter.  Their  chief  incidence  in  the  brain  is  in 
the  centrum  ovale,  the  basal  ganglia,  the  pons  and  medulla, 


286 


DISSEMINATED  SCLEROSIS 


Fig.  98. 
Disseminated  sclerosis.     Sections  of  pons  and  medulla. 


DISSEMINATED  SCLEROSIS 


287 


J 

1 

.if  ■ 

-^i^ 

5> 

€) 

Fig.  99. 

Disseminated  sclerosis.      Sections   of   cerebellar  cortex   and   of   cord    (one 
longitudinal  and  several  transverse  at  various  levels  in  the  same  cord). 


288  DISSEMINATED  SCLEROSIS 

where  they  often  seem  to  spread  out  from  the  walls  of  the 
ventricles.  All  parts  of  the  cord  appear  to  be  equally 
affected.  Most  observers  agree  that  the  cerebellar  lobes  are 
comparatively  rarely  attacked.  The  optic  nerve  suffers  more 
frequently  than  any  other  cranial  nerve.  Patches  have  also 
been  discovered  occasionally  in  the  ventral  and  dorsal  spinal 
nerve  roots.  A  good  general  idea  of  the  distribution,  size 
and  shape  of  the  islets  of  sclerosis  can  best  be  obtained  by 
staining  a  number  of  sections  transversely  and  longitudinally 
from  different  levels  of  the  central  nervous  system  by  means 
of  the  Weigert-Pal  method.  The  examination  of  such  a  series 
of  sections  brings  into  prominence  the  notable  absence  of 
deformity  resulting  from  the  presence  of  the  sclerosis.  It 
also  serves  to  emphasise  what  is  one  of  the  most  striking 
features  of  this  disease — namely,  the  comparatively  small 
amount  of  secondary  degeneration  which  results  from  the 
morbid  process.  In  our  experience,  secondary  degeneration 
in  the  long  tracts  of  the  spinal  cord  is  not  quite  so  un- 
common as  some  observers  suggest,  but  the  discrepancy  is 
probably  explained  by  the  fact  that  secondary  degeneration 
only  occurs  when  the  long  fibres  of  a  particular  tract  have  been 
exposed  at  various  levels  to  numerous  or  perhaps  unusually 
severe  attacks.  This  explanation  appears  to  be  confirmed 
by  clinical  experience  in  a  way  which  will  be  referred  to 
below. 

If  the  patch  be  old,  no  trace  of  myelin  will  be  contained  within 
its  area.  If,  on  the  other  hand,  it  is  of  more  recent  origin,  the 
Marchi  method  may  reveal  more  or  less  numerous  droplets  of 
altered  myelin,  either  in  the  medullary  sheaths  or  in  the  sub- 
stance of  compound  granular  corpuscles.  Such  fatty  masses, 
stained  a  deep  brown  or  black  tint,  may  sometimes  be 
seen  collected  in  the  immediate  neighbourhood  of  the  blood 
vessels.  The  axis  cylinders  may  be  shown  in  many  cases,  by 
Bielschowsky's  impregnation  method,  to  remain  intact, 
although  deprived  of  their  medullary  sheaths.  They  pass 
unaltered  through  the  islet  of  sclerosis.  In  other  instances  the 
axis  cylinders  do  not  present  an  altogether  healthy  appearance. 
They  may  be  swollen,  varicose,  fusiform,  or  generally  thinned 
and  atrophied  in  appearance.  The  changes  in  the  neuroglia 
vary  considerably  in  different  patches,  and  depend  probably 


DISSEMINATED  SCLEROSIS  289 

to  a  large  extent  upon  the  age  of  the  particular  plaque  examined. 
In  some,  probably  the  older  plaques,  there  is  a  thick  network  of 
neuroglial  fibres  and  a  sparsity  of  glial  cells.  In  other  patches 
the  glial  cells  are  more  plentiful,  and  the  ground  substance 
shows  a  more  finely  granular  structure  and  a  more  open  network 
of  fibres.  The  blood  vessels  seen  in  the  diseased  area  may 
present  a  perfectly  normal  appearance.  On  the  other  hand, 
there  may  be  indications  of  subacute  inflammatory  changes. 
For  instance,  the  perivascular  spaces  may  be  dilated  and  contain 
lymphocytic  and  leucocytic  cells  of  various  sizes.  In  other 
patches  the  vessel  walls  may  be  notably  thickened  and  show 
evidence  of  hyaline  degeneration.  When  a  patch  reaches  the 
surface  the  adjacent  pia  mater  may  be  more  adherent  to  the 
medullary  tissue  than  is  normally  the  case,  and  may  show  a 
certain  amount  of  unnatural  opacity  due  to  proliferation  of 
the  connective- tissue  elements. 

It  is  surprising  how  little  the  ganglion  cells  included  in  a 
sclerotic  area  may  suffer,  and  in  many  cases  it  is  impossible  to 
say  that  any  changes  are  present.  Occasionally  chromatolytic 
alterations  can  be  detected,  and  still  more  rarely  there  is 
an  obvious  diminution  in  the  number  of  the  cells.  Too 
much  importance  must  not  be  attached  to  the  presence  of 
pigmentation,  which  is  always  of  doubtful  pathological 
significance. 

Relationship  of  anatomi  al  to  clinial  phenomena. — The 
clinical  course  of  disseminated  sclerosis  is  characterised  by 
the  occurrence  of  exacerbations  and  remissions.  The  sudden 
loss  of  power  in  a  limb  or  equally  sudden  loss  of  sight  in  one 
eye  may  be  the  first  symptom,  and  the  recovery  may  be  so 
complete  in  the  course  of  a  few  weeks  that  an  hysterical  origin 
for  the  trouble  is  suspected.  Other  attacks  follow  at  varying 
intervals,  with  the  result  that,  although  partial  recovery 
always  ensues,  each  leaves  the  patient  somewhat  more 
disabled. 

This  clinical  fact  may  be  readily  understood  if  we  regard  each 
attack  as  the  effect  of  an  inflammatory  patch  in  the  central 
nervous  system  which,  while  temporarily  impairing  the  con- 
ducting power  of  the  nerve  fibres,  does  not  destroy  the  axis 
cylinders.     The  latter  are  denuded  of  their  myelin  sheaths, 

but  with  subsidence  of  the  inflammation  regain  their  function 

19 


290  DISSEMINATED  SCLEROSIS 

either  completely  or  to  a  very  considerable  degree.  In  the 
course  of  time,  however,  the  fibres  of  a  particular  tract  are 
subjected  to  many  pathological  insults  at  different  levels,  and 
so  tend  to  be  permanently  injured.  In  this  way  symptoms 
referable  to  disease  of  certain  tracts  become  constant  and  the 
spastic  paraplegia,  which  is  so  common  a  feature  of  the  disease, 
is  easily  accounted  for.  Similarly  the  ataxy  of  limbs,  which 
is  another  frequent  symptom,  may  be  brought  into  line  with 
patches  of  sclerosis  affecting  the  dorsal  columns  and  cere- 
bellar tracts  at  various  levels.  The  cranial  nerve  symptoms, 
particularly  the  optic  atrophy,  have  the  same  origin.  Oc- 
casionally optic  neuritis,  which  represents  an  affection  of  the 
optic  disc,  may  be  observed.  On  the  other  hand,  the  absence 
of  lower  motor  neuron  disturbances — in  other  words,  the 
absence  of  muscular  atrophy — is  due  to  the  integrity  of  the 
ventral  horn  cells  even  when  they  are  included  in  a  diseased 
area. 

4.  Syringomyelia. 

Syringomyelia  is  a  chronic  and  usually  progressive  disease  of 
the  spinal  cord,  characterised  anatomically  by  the  presence  of 
one  or  more  pathological  cavities.  It  is  more  commonly  found 
in  men  than  in  women,  and  the  average  age  at  which  the 
symptoms  first  show  themselves  is  somewhere  between  twenty 
and  thirty.  With  the  spinal  disease,  which  is  frequently 
regarded  as  congenital  in  origin,  other  congenital  anomalies 
are  often  associated.  For  instance,  the  patient  may  be  unduly 
small  or  infantile  in  his  proportions,  presenting  a  large  head 
with  diminutive  trunk  and  limbs;  or  he  may  have  unusual 
deformities  of  the  skull,  of  the  bones,  of  the  limbs  or  of  the 
vertebral  column,  such  as  a  spina  bifida.  Cases  of  combined 
acromegaly  and  syringomyelia  have  been  recorded  sufficiently 
often  to  make  the  association  interesting. 

Pathogenesis. — The  number  of  theories  which  have  been  put 
forward  to  explain  the  origin  of  the  morbid  process  underlying 
syringomyelia  suggests  that  various  cases  of  spinal  cavita- 
tion, although  roughly  resembling  one  another,  may  have 
different  sources.  It  is  impossible  to  elaborate  a  genetic  theory 
applicable  to  every  case,  and  brief  reference  must  be  made  to 
certain   developmental,    anatomical    and    pathological    facts 


SYRINGOMYELIA  291 

which  may  throw  some  light  on  particular  examples  of  the 
disease. 

(a)  Developmental. — The  medullary  canal  of  early  foetal 
life  is  only  represented  clearly  in  the  child  by  the  central  canal 
of  the  cord,  which  is  a  cylindrical  tube  lined  by  ependymal 
cells  of  epiblastic  origin  running  throughout  the  length  of 
that  organ.  This  central  canal,  however,  represents  only  the 
ventral  limb  of  the  medullary  canal,  the  dorsal  and  lateral 
limbs  disappearing  as  the  dorsal  columns  of  either  side 
gradually  coalesce  in  the  region  of  the  dorsal  median  fissure. 
Under  normal  conditions  there  are  no  cells  resembling  the 
ependymal  cells  of  the  central  canal,  either  in  the  lateral 
parts  of  the  grey  commissure,  in  the  bases  of  the  dorsal  horn, 
or  in  the  walls  of  the  dorsal  median  fissure.  It  is  not  unreason- 
able, however,  to  suppose  that  in  some  cases  there  may  be  in 
these  three  contiguous  parts  embryonic  remnants  capable  of 
renewed  activity,  and  so  of  produfcing  neuroglia  which  is  the 
most  primitive  tissue  of  epiblastic  origin  in  the  central 
nervous  system.  Since  the  neuroglial  hyperplasia  or  gliomatosis 
of  syringomyelia  nearly  always  originates  either  in  the  grey 
commissure,  the  bases  of  the  dorsal  horn,  or  in  the  ventral 
third  of  the  dorsal  columns,  its  source  may  justifiably  be 
connected  with  the  developmental  process  just  referred  to. 
The  occasional  presence  of  groups  of  ependymal  cells  away 
from  the  central  canal  in  otherwise  normal  cords  may  be 
regarded  as  a  congenital  accident  which,  under  certain 
stimulating  conditions,  might  give  rise  to  a  peri-ependymal 
hyperplasia  of  the  glial  tissues  just  as  such  hyperplasia  certainly 
originates  in  some  instances  from  the  walls  of  the  central  canal 
itself. 

[h)  Anatomical. — A  consideration  of  the  spinal  vascular 
supply  brings  out  one  important  point.  That  part  of  the  spinal 
cord  which  includes  the  grey  commissure,  the  ventral  third 
of  the  dorsal  columns,  and  the  bases  of  the  dorsal  horns, 
is  the  centre  of  the  cord  from  a  vascular  point  of  view.  It 
receives  blood  from  various  radiating  vessels,  of  which  the 
most  important  are  those  entering  along  the  dorsal  roots  and 
along  the  dorsal  septum,  as  well  as  from  some  of  the  terminal 
branches  of  the  ventral  spinal  arteries.  It  contains,  therefore, 
vessels  of  small  calibre,  some  of  which  have  a  transverse  and 


292  SYRINGOMYELIA 

some  a  longitudinal  course.  This  fact  is  important  in  two 
ways.  In  the  first  place,  any  general  disease  of  the  spinal 
arteries  which  impairs  the  elasticity  of  their  walls  will  produce 
its  greatest  effect  on  the  circulation  within  the  central  zone. 
In  the  second  place,  any  morbid  process  leading  to  pressure 
upon,  or  strangulation  of,  the  pial  vessels  on  the  dorsal 
surface  of  the  cord  will  have  a  profound  effect  upon  the  blood 
supply  of  the  same  area.  In  the  same  way  the  central  zone 
of  the  spinal  cord  is  supplied  by  lymphatics  entering  with  the 
dorsal  roots.  For  this  reason,  some  exceptional  cases  of 
syringomyelia  have  been  regarded  as  infective  in  origin,  the 
infection  being  carried  in  along  these  lymph  channels,  and 
perhaps  being  further  spread  by  the  fluid  of  the  central  canal. 
The  closure  of  the  central  canal  at  one  level  of  the  cord  has 
been  suggested  as  a  sufficient  reason  to  explain  dilatation  of 
that  canal  at  other  levels.  Such  an  explanation  is  open  to 
question  when  it  is  remembered  that  in  normal  adult  cords 
the  canal  may  be  obliterated  in  some  segments,  and  yet  patent 
without  dilatation  above  and  below. 

(c)  Pathological. — The  partiality  of  intramedullary  haemor- 
rhages and  abscesses  to  make  a  track  from  segment  to  segment 
along  the  tissues  at  the  base  of  the  dorsal  horn  in  the  central 
grey  matter  is  so  striking  that  this  area  has  been  termed  the 
zone  of  least  resistance.  The  fact  that  gliomatosis  spreads 
along  similar  lines  has  led  to  the  belief  that  some  cases  of 
syringomyelia  have  their  remote  origin  in  spinal  haemorrhage 
occurring  at  birth.  It  is  possible,  therefore,  although  not 
proved,  that  an  old  pathological  process  may,  after  a  con- 
siderable lapse  of  time,  be  the  starting-point  for  gliomatosis. 

These  developmental,  anatomical  and  pathological  data 
taken  into  consideration  with  clinical  observations  suggest 
that  various  influences  are  at  work  in  the  production  of  spinal 
cavities.  Thus  there  are  cases  in  which  a  congenital  defect 
appears  to  carry  great  weight;  others  in  which  a  morbid 
condition  of  the  vascular  supply,  produced  perhaps  by  a 
chronic  meningitis  on  the  dorsal  surface  of  the  cord,  seems 
too  important  to  overlook;  and  others,  again,  in  which  some 
chronic  lymphatic  infection  or  a  history  of  some  traumatic 
haematomyelia  require  to  be  taken  into  consideration.  The 
fact  that  gliomatosis  is  always  associated  in  greater  or  less 


SYRINGOMYELIA  293 

degree  with  the  formation  of  cavities  is  best  explained  by  the 
tendency  of  ghomatous  tissues  after  reaching  a  certain  bulk 
to  undergo  central  degeneration,  which  tendency  is  doubtless 
promoted  by  the  deficiency  in  its  blood  supply. 

With  regard  to  the  ordinary  cases  of  chronic  progressive 
syringomyelia,  which  form  the  majority  of  those  with  typical 
clinical  features,  little  hesitation  can  be  felt  in  placing  fore- 
most some  congenital  anomalies  of  the  central  embryonic  tissue, 
the  latent  activity  of  which  is  prone  to  display  itself  during  the 
early  years  of  adult  life  in  the  form  of  a  slow-growing  hyper- 
plasia, having  some  of  the  characters  of  a  benign  neoplasm 
and  strong  tendencies  towards  the  formation  of  cavities. 

Morbid  anatomy. — The  spinal  cord  appears  altered  in  shape, 
often  very  irregularly.  In  most  instances  the  cervico-thoracic 
region  is  enlarged  and  flattened,  the  lateral  dimension  being 
increased  out  of  proportion  to  the  antero-posterior.  Some- 
times the  deformity  may  extend  as  high  as  the  medulla  or  even 
the  pons,  and  in  other  cases  may  involve  a  large  part  of  the 
thoracic  region.  The  lumbo-sacral  region  is  occasionally  the 
site  of  the  greatest  change.  The  meninges  in  the  majority  of 
cases  present  no  abnormality ;  in  others  there  may  be  a  definite 
chronic  meningitis,  probably  of  syphilitic  origin.  The  ventral 
spinal  roots  at  the  level  of  the  greatest  deformity  may  be 
atrophied  and  translucent  in  appearance.  On  palpation  the 
swollen  parts  are  soft  and  usually  flaccid.  The  narrow  parts 
may  be  normal  in  consistence  or  suggest  to  the  palpating  finger 
the  presence  of  a  hard  core  lying  within  an  outer  ring  of  more 
normal  tissue.  A  series  of  transverse  slices  demonstrates 
striking  changes  which  vary  in  appearance  at  different 
levels.  In  the  region  of  the  greatest  swelling,  usually  the 
cervico-thoracic  region,  the  cross-section  appears  at  first 
sight  to  have  traversed  an  area  of  necrotic  softening,  but 
closer  investigation  shows  that  near  the  centre  of  the 
cord  is  a  cavity  from  which  clear  fluid  may  be  oozing, 
and  that  this  cavity  is  surrounded  by  a  mass  of  gelatinous 
material  either  pale  and  translucent  or  yellowish-brown, 
according  to  the  amount  of  altered  blood  pigment  it  contains. 
The  actual  wall  of  the  cavity  sometimes  stands  out  as  an 
opaque  yellow  membrane  which  has  been  thrown  into  folds  by 
the  escape  of  fluid  and  the  collapse  of  the  surrounding  parts. 


Fig.  ioo. 

Syringomyelia,  a,  Note  the  excessive  gliomatosis  and  the  invasion  of  the 
grey  matter  from  the  dorsal  columns,  b,  The  cavity  is  distinct  from  the 
central  canal,  c,  The  cavity  has  a  very  well-defined  lining  membrane.  Note 
the  descending  degeneration  in  the  lateral  columns.  (Compare  with 
Fig.  12.) 


SYRINGOMYELIA  295 

Further  sections  at  different  levels  will  display  the  length  of 
the  cavity  and  sometimes  the  presence  of  more  than  one  cavity. 
Rarely  the  tube  is  prolonged  into  the  fourth  ventricle,  although 
in  one  case  it  extended  as  far  as  the  right  internal  capsule. 
When  two  cavities  are  present  side  by  side  it  is  the  rule  to  find 
on  further  investigation  that  one  is  an  offshoot  of  the  other. 

The  syringomyelic  cavity  generally  lies  behind  the  ventral 
commissure  either  in  the  grey  matter  near  the  central  canal 
or  more  laterally  in  the  base  of  one  or  other  dorsal  horn. 
Diverticula  in  various  directions  are  common  enough  and 


Fig.  ioi. 
Syringobulbia. 

produce  varieties  in  the  shape  of  the  cavity  at  different  levels. 
The  general  result  is  to  produce  asymmetry  rather  than 
symmetry  in  the  relation  of  the  two  halves  of  the  cord  to  one 
another. 

In  the  medulla,  as  in  the  spinal  cord,  the  morbid  process  has  a 
favourite  site.  Frequently  the  only  evidence  of  disease  in  this 
region  is  the  presence  of  one  or  more  fissures  originating  in  the 
floor  of  the  fourth  ventricle  a  little  to  one  side  of  the  mid-line, 
and  extending  forward  and  outward  in  such  a  way  as  to  cut 
off  the  restiform  body  from  the  central  parts  of  the  medulla. 


296  SYRINGOMYELIA 

Such  a  fissure  may  destroy  the  descending  root  of  the  fifth 
nerve,  the  sohtary  fasciculus,  and  some  of  the  nuclei  belonging 
to  the  vago-glossal  pharyngeal  nerves. 

The  disposition  of  the  surrounding  gliomatous  tissue  follows 
roughly  the  various  diverticula,  forming  prolongations  of 
its  own  and  extending  to  levels  beyond  the  limits  of  the 
cavity.  The  gliomatous  tissue  varies  greatly  in  thickness. 
It  may  present  the  characters  of  a  thin  lining  membrane 
to  a  large  cavity,  or  it  may  be  so  voluminous  as  to 
overshadow  the  narrow  slit-like  tube  it  contains.  The 
gelatinous-looking  material  is  composed  of  fibres  and  cells 
in  varying  proportion.  There  are  generally  more  cells  than 
in  normal  neuroglial  tissue,  and  less  cells  than  in  a  true 
glioma.  The  glial  tissue  may  actually  form  the  wall  of  the 
cavity  or  may  be  separated  from  its  lumen  by  a  narrow  border 
of  ependymal  cells.  The  peripheral  parts  of  the  gliomatous  mass 
merge  into  the  more  normal  neuroglia  and  nerve  tissues.  Often 
when  there  is  no  central  cavity  there  may  be  areas  of  softening 
containing  finely  granular  or  homogeneous  material. 

The  syringomyelic  cavity  may  sometimes  represent  the 
central  canal,  but  more  often  is  found  distinct  from  the  latter. 
In  some  instances  the  cavity  is  fused  with  the  central  canal 
over  several  segments  and  separated  from  it  in  regions  beyond. 

The  blood  vessels  of  the  cord  are  often  perfectly  healthy,  but 
in  other  cases  those  which  radiate  from  the  surface  into  the 
central  gliomatous  tissue  show  hyaline  and  other  degenerative 
changes.  The  lumen  may  be  diminished  or  obliterated,  es- 
pecially when  it  reaches  the  glial  mass,  and  in  the  neighbourhood 
of  the  cavity  the  remnant  of  a  vessel  may  be  represented  by 
an  undulating  ribbon  of  hyaline  connective  tissue,  which  has 
been  unfortunately  called  a  papillary  membrane.  Old  or  recent 
haemorrhages  are  not  infrequent,  and  the  pigment  may  give 
a  brownish  tinge  to  the  tissues. 

The  effects  of  gliomatosis  and  cavitation  are  due  in  part  to 
pressure  and  in  part  to  direct  invasion.  The  latter  method 
is  the  one  by  which  the  dorsal  columns  are  principally 
affected,  the  new-formed  tissue  eating  its  way,  as  it  were, 
between  the  bundles  of  nerve  fibres  and  causing  their  slow 
destruction.  Pressure  leads  to  the  production  of  oedema 
around  the  glial  mass,  and  this  is  often  responsible  for  the 


SYRINGOMYELIA  297 

rarefaction  of  the  grey  matter  of  the  ventral  horns.  The 
nerve  cells  become  isolated  and  their  processes  disappear,  with 
the  result  that  a  species  of  cavity  may  be  formed  to  which  the 
name  "  perigHomatous  "  as  opposed  to  "  endogliomatous  "  has 
been  given.  Secondary  degenerations  in  the  pyramidal  tracts, 
in  the  dorsal  columns  and  in  the  ascending  ventro-lateral 
tracts,  are  of  common  occurrence,  and  are  mainly  produced 
by  pressure  on  those  regions. 

Secondary  degenerative  changes  occur  in  other  tissues,  such 
as  the  nerves,  muscles,  skin,  joints,  and  bones,  but  do  not  present 
features  which  are  peculiar  to  this  disease. 

Some  reference  must  be  made  to  the  not  infrequent  con- 
currence of  a  true  neoplasm  with  the  syringomyelic  process. 
At  any  level  of  the  cord,  commonly  in  the  cervical  region,  may 
be  found  a  true  tumour  involving  more  or  less  the  entire 
transverse  area,  which  has  evidently  originated  from  a  part 
of  the  gliomatous  mass.  Such  tumours  may  be  very  cellular 
gliomata,  vascular  angiogliomata,  or  more  rarely  sarcomata. 

The  relation  of  the  anatomical  to  the  clinical  phenomena. — 
The  fact  that  the  cervico-thoracic  region  of  the  cord  is  generally 
the  site  of  most  change  explains  the  frequency  of  a  particular 
type  of  syringomyelia,  which  is  characterised  by  an  atrophic 
palsy  beginning  in  the  hands  and  forearms  and  a  spastic 
paralysis  of  the  trunk  and  legs.  The  muscular  atrophy  is,  of 
course,  the  result  of  the  secondary  effects  on  the  ventral  grey 
matter  described  above,  and  the  spastic  paraplegia  is  due  to  the 
interference,  chiefly  by  pressure,  with  the  pyramidal  tracts. 
The  characteristic  dissociative  anaesthesia  of  syringomyelia 
can  be  explained  by  the  incidence  of  the  disease  on  the  central 
parts  of  the  cord.  There  is  reason  to  believe  that  the  fibres 
conducting  thermal  and  painful  impulses  cross  from  one  side 
to  the  other  in  the  grey  commissure,  whereas  those  carrying 
tactile  impulses  are  represented  both  in  the  lateral  and  the 
dorsal  columns,  and  are  thus  less  profoundly  influenced  by  a 
central  lesion  at  any  particular  level.  The  trophic  changes  in 
bones,  joints,  and  skin  in  this  disease  have  not  yet  received  a 
complete  pathological  explanation,  and  can  hardly  be  brought 
into  relationship  with  the  anatomical  changes  in  the  spinal  cord 
at  the  present  time. 


298  PARALYSIS  AGITANS 

5.  Paralysis  Agitans  (Parkinson's  Disease). 

This  is  a  slowly  progressive  disease  of  unknown  causation, 
usually  beginning  in  middle  life  or  later,  but  in  a  minority 
of  cases  in  the  second  or  third  decade.  It  is  characterised 
by  the  three  cardinal  symptoms  of  tremor,  rigidity  and 
weakness.  Usually  all  the  limbs,  as  well  as  the  face,  neck 
and  trunk,  are  affected,  but  at  first  the  disability  is  hemiplegic 
or  monoplegic  in  distribution,  and  may  remain  for  many 
years  more  pronounced  on  one  side. 

Morbid  anatomy. — For  a  long  time  the  site  of  the  lesion  in 
this  disease  was  unknown,  but  a  number  of  cases  examined 
during  the  past  few  years  have  presented  changes  in  the 
corpus  striatum.  The  earliest  worker  to  observe  changes  in 
this  region  was  Jelgersma,  who,  in  1908,  reported  a  case 
with  atrophy  of  certain  tracts  leading  from  the  corpus 
striatum  to  the  mid-brain.  This  observation  has  been 
largely  confirmed  by  subsequent  writers,  some  of  whom 
have  found  areas  of  rarefaction  or  softening  in  the  corpus 
striatum. 

In  1917  Ramsay  Hunt,  in  the  examination  of  a  case  of  the 
juvenile  form  of  the  disease  which  started  in  the  second  decade, 
found  that  the  essential  lesion  was  a  primary  atrophy  of  the 
large  cells  of  the  "  pallidal  system."*  These  were  greatly 
reduced  in  numbers,  and  the  remaining  cells  showed  various 
stages  of  chromatolytic  degeneration  often  associated  with 
neuronophagy.  Along  with  this  there  was  a  great  increase 
in  the  number  of  glial  cells  in  the  affected  areas.  Except  for 
a  moderate  thickening  of  the  walls  of  the  blood  vessels  in 
certain  areas,  no  vascular  changes  were  present  to  account 

*  According  to  Hunt  the  cells  of  the  pallidal  system  are  large  multipolar  cells 
found  chiefly  in  the  globus  pallidus,  but  also  scattered  among  the  smaller  cells 
of  the'putamen,  caudate  nucleus  and  basal  nucleus  of  Meynert.  In  histological 
appearances  they  resemble  the  large  motor  cells  of  the  ventral  horns  and  the 
Betz  cells  of  the  precentral  convolution.  They  represent  an  alternative  motor 
system  to  the  pyramidal  system,  than  which  they  are  phylogenetically  older, 
being  present  in  the  lower  forms  of  fishes.  They  are  connected  with  the  optic 
thalamus  through  the  medium  of  the  smaller  cells  of  the  corpus  striatum,  but 
apparently  have  no  direct  connection  with  the  cortex  or  the  internal  capsule. 
Their  efferent  fibres  run  in  the  ansa  system — the  ansa  radiations,  ansa 
lenticularis  and  ansa  peduncularis.  Kinnier  Wilson  has  divided  these  fibres 
into  two  groups  :  (i)  coarser  fibres  which  run  transversely  to  end  in  the 
ventral  and  lateral  surface  of  the  thalamus  and  in  the  nucleus  ruber;  (2) 
smaller  fibres  which  terminate  in  the  corpus  Luysii,  the  nucleus  ruber  and 
the  substantia  nigra. 


PARALYSIS  AGITANS  299 

for  the  cell  degeneration,  which  he  considered  to  be  a  primary 
atrophy.  All  other  parts  of  the  brain  and  brain-stem  were 
normal.  The  tracts  leading  from  the  corpus  striatum  to  the 
mid-brain  showed  some  thinning  of  the  fibres  composing  them, 
but  there  was  no  such  definite  tract  degeneration  as  is  seen, 
for  example,  in  hemiplegia.  This  case  suggests  that  the 
symptoms  of  paralysis  agitans  may  be  due  to  a  primary 
progressive  atrophy  of  the  cells  of  the  pallidal  system. 
More  recently  Hunt  has  reported  the  results  of  examining 
two  cases  of  the  ordinary  presenile  form  of  the  disease, 
which  also  showed  degeneration  of  the  pallidal  system  of 
cells. 

In  some  cases  the  degeneration  may  be  a  form  of  primary 
atrophy,  associated  with  some  toxic  absorption  or  error  of 
metabolism.  In  others,  it  is  a  senile  atrophy  due  to 
abiotrophy  or  to  vascular  disease.  The  clinical  picture  of 
paralysis  agitans  may  be  produced  by  gross  lesions,  such  as 
encephalitis,  haemorrhage,  softening  or  tumour,  affecting 
the  globus  pallidus  of  the  lenticular  nucleus. 

Relation  of  anatomical  with  clinical  phenomena. — The  pallidal 
system  of  cells  seems  to  have  some  connection  with  the  faculty 
of  synergic  movement,  which  is  preserved  in  lesions  of  the 
pyramidal  system,  whereas  its  loss  constitutes  one  of  the  chief 
disabilities  of  paralysis  agitans.  The  festinant  gait,  and  the 
phenomena  of  propulsion  and  retropulsion,  are  connected 
with  this  loss. 

The  peculiar  tremor  of  the  disease  has  long  been  associated 
with  mid-brain  lesions. 

6.  Myasthenia  Gravis. 

Aetiology. — The  essential  cause  of  this  disease  is  still  a  matter 
of  speculation,  and  the  various  theories  which  have  been  pro- 
pounded are  not  based  on  substantial  foundations.  Age  has 
but  little  influence,  although  the  majority  of  cases  occur  in  the 
third  and  fourth  decades  of  life.  Both  sexes  are  attacked  in 
about  equal  proportion.  There  are  no  familial  or  hereditary 
tendencies.  The  onset  of  symptoms  may  follow  infective 
fevers,  exertion,  chills,  and  emotions,  but  not  more  frequently 
than  may  be  explained  by  the  laws  of  coincidence.  Although 
some  victims  of  the  disease  have  presented  abnormalities,  such 


300  MYASTHENIA  GRAVIS 

as  bifid  uvula,  Polydactyly  and  webbing  of  the  toes,  there  is 
not  sufficient  evidence  to  justify  emphasis  being  laid  on  the 
presence  of  congenital  defects. 

Pathogenesis. — Numerous  hypotheses  have  been  put  forward 
to  throw  light  on  the  obscurity  in  which  the  pathogenesis  of 
myasthenia  gravis  is  shrouded.  Before  any  morbid  anatomy 
had  been  recognised,  it  was  regarded  as  a  neurosis  of  congenital 
origin.  With  the  discovery  of  enlarged  thymus  glands  in 
certain  cases,  there  was  a  natural  inclination  to  assume  that 
poisons  produced  by  them  and  capable  of  modifying  nervous 
and  muscular  function  were  thrown  into  the  circulation.  This 
view  has  been  upset  by  the  fact  that  many  cases  of  the  disease 
do  not  present  any  abnormalities  in  connection  with  the 
thymus  gland.  Other  observers  have  found  congestion  and 
enlargement  of  the  parathyroids,  and  consider  myasthenia  to 
be  due  to  hyperactivity  of  these  organs.  The  influence  of  the 
parathyroids  on  the  functional  activity  of  muscles  is  shown 
by  experimental  tetany  which,  on  this  theory,  is  the  converse 
of  myasthenia. 

One  author  maintains  that  the  disease  is  characterised  by 
hyperoxygenation,  which  is  shown  especially  in  connection  with 
voluntary  movements,  and  which  results  in  the  production  of 
chemical  alterations  in  the  musculature  owing  to  some  inter- 
ference with  the  formation  of  antibodies  of  fatigue.  It  has 
been  suggested,  on  the  other  hand,  that  the  clinical  manifesta- 
tion of  muscular  fatigue  may  possibly  be  explained  by  as- 
suming a  diminished  functional  activity  on  the  part  of  the 
sarcoplasmic,  as  compared  to  the  fibrillar,  elements  of  the 
muscles,  with  the  result  that  the  fibrillar  constituents,  acting 
at  a  disadvantage,  become  readily  and  rapidly  exhausted  when 
excited  by  the  will  or  by  the  faradic  current. 

No  pathogenetic  theory  can  afford  to  neglect  the  oft-con- 
firmed observation  that  women  who  suffer  from  myasthenia 
may  lose  all  their  symptoms  during  pregnancy,  only  to  relapse 
into  their  former  condition  after  confinement.  Although  this 
is  not  an  invariable  rule,  it  is  sufficiently  common  to  indicate 
that  the  foetal  tissues  may  temporarily  provide  some  substance 
which  either  counteracts  a  circulating  poison  or  supplies  a 
deficiency  in  the  body  of  the  mother. 

We  may  not  be  wrong  in  supposing  that  some  disturbance  of 


MYASTHENIA  GRAVIS  301 

glandular  function  is  responsible  for  a  modification  of  muscular 
activity,  and  for  such  sensory  and  mental  symptoms  as  are 
occasionally  met  with  in  myasthenic  patients. 

Morbid  anatomy. — The  absence  of  obvious  and  constant 
changes  in  the  nervous  system  in  cases  of  myasthenia  gravis 
is  now  generally  acknowledged,  and  the  only  characteristic 
feature  is  the  presence  of  cellular  deposits  in  many  and  various 
organs  of  the  body,  and  particularly  in  the  skeletal  muscles. 
Reference  must  also  be  made  to  certain  abnormalities  of 
the  thymus  gland  which  only  occur,  however,  in  a  certain 
percentage  of  cases. 

In  the  central  nervous  system  developmental  defects  have 
been  noted  in  rare  instances,  and  a  very  few  observers  have 
recorded  slight  chromolytic  changes  in  ganglion  cells.  As  a 
rule,  examination  of  the  nervous  system  reveals  a  perfectly 
normal  condition.  Small  deposits  of  mononuclear  cells 
{lymphorrhages)  have  been  observed  in  the  spinal  root  ganglia, 
the  medulla  and  elsewhere,  but  their  occurrence  is  relatively 
infrequent  when  compared  to  that  of  similar  deposits  in  the 
muscles.  Recent  capillary  haemorrhages,  when  present,  are 
the  result  of  the  respiratory  embarrassment  which  so  commonly 
brings  about  the  fatal  termination  of  the  disease. 

Lymphorrhages  are  more  commonly  described  in  the  muscles 
than  in  other  organs,  possibly  because  they  have  been  more 
thoroughly  investigated.  The  constituent  cells  are  found  in 
ill-defined  clumps  between  the  muscle  fibres  and  generally  in 
the  vicinity  of  a  capillary  vessel.  There  may  be  a  serous  as  well 
as  a  cellular  exudate.  The  size  of  a  lymphorrhage  varies  con- 
siderably ;  it  may  be  very  minute  or  large  enough  to  be  detected 
in  a  stained  section  by  the  naked  eye.  Lymphorrhages  have 
been  demonstrated  in  many  muscles,  especially  the  ocular 
muscles,  and  also  in  the  myocardium,  but  it  may  be  necessary 
to  examine  very  many  sections  in  order  to  prove  their  existence. 
Speaking  generally,  the  neighbouring  muscle  fibres  are  healthy, 
but  occasionally  they  have  undergone  degenerative  changes, 
and  have  been  even  invaded  by  the  lymphocytes.  In  addition 
to  the  presence  of  lymphorrhages  the  muscle  fibres  are  wont 
to  display  early  changes  in  the  form  of  plasmatic  swelling, 
proliferation  of  nuclei,  hyaline  and  granular  degeneration. 
In   other  cases  there   has   been  distinct   muscular  atrophy, 


302 


MYASTHENIA  GRAVIS 


#*       *» 


Aly  isths/iia  gfavis.  a,  Drawing  of  transverse  section  of  an  ocular  muscle 
showing  a  "  lymphorrhage."  b,  Photograph  of  tranverse  section  of  a  skeletal 
muscle. 


MYASTHENIA  GRAVIS  303 

resembling  that  seen  in  progressive  muscular  atrophy  of  the 
spinal  type. 

The  thymus  gland  is  often  the  seat  of  morbid  changes; 
sometimes  it  is  only  represented  by  the  remnants  of  lymphatic 
tissue  characteristic  of  the  organ  in  adult  life.  The  abnormali- 
ties are  not  specific,  and  may  be  divided  into  three  classes: 
(i)  simple  hypertrophy,  (2)  hypertrophy  with  degenerative  and 
proliferative  changes,  and  (3)  new  growth.  In  the  first  class 
may  be  included  those  cases  in  which  the  gland,  not  having 
undergone  the  ordinary  regressive  changes,  is  as  large  or  larger 
than  that  of  infants.  It  may  be  histologically  normal  or 
lacking  in  eosinophil  cells.  Large  glands  with  multilocular 
cysts  are  instances  of  the  second  class.  New  growths  are 
represented  by  lympho-sarcomata  and  other  rarer  forms  of 
neoplasm. 

The  thyroid  gland  has  been  found  to  be  the  site  of  lymphor- 
rhages,  interstitial  fibrosis,  colloid  degeneration  of  the  fibrous 
stroma,  and  proliferation  of  the  epithelium  with  formation 
of  new  vesicles.  The  pituitary  body  has,  in  one  case,  presented 
a  large  adenoma.  The  liver  may  be  the  seat  of  numerous 
lymphorrhages,  especially  in  the  neighbourhood  of  the  biliary 
ducts.  Serous  as  well  as  cellular  exudation  is  often  found,  and  a 
moderate  degree  of  fatty  change  in  the  hepatic  tissue  has  been 
observed.  The  adrenals,  the  kidneys,  the  lungs,  and  the 
pancreas  have  all  been  known  to  contain  lymphorrhages,  but 
other  abnormalities  are  rare.  The  bone  marrow  is  free 
from  notable  changes,  and  the  blood  and  cerebro-spinal 
fluid  have  been  repeatedly  searched  in  vain  for  abnormal 
features. 

The  relation  of  clinical  to  anatomical  phenomenon. — We  are 
too  ignorant  at  present  of  the  exact  nature  of  this  disease  to 
draw  any  important  deductions.  Lymphorrhages  are  certainly 
not  the  cause  of  the  alteration  in  muscular  function,  but  the 
slight  degenerative  changes  in  the  fibres  may  confirm  the  im- 
pression, gained  from  clinical  experience,  that  the  character- 
istic exhaustion  is  of  muscular  rather  than  of  nervous  origin. 
This  is  also  supported  by  the  absence  of  constant  changes  in 
the  nervous  tissues. 


304  DISEASES  OF  OBSCURE  ORIGIN 


REFERENCES 

Motor  Neuron  Disease. 

Beevor,  C.  E.,  Batten,  F.  E.,  and  Holmes,  G.  :  Allbutt  and  Rolleston,  System 
of  Medicine,  vol.  vii.,  1910,  p.  699. 

Subacute  Combined  Degeneration. 

Collier.  James:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910, 
p.  786. 

Disseminated  Sclerosis. 

Da  Fano,  C:  Journ.  New.  and  Ment.  Dis.,  1920,  vol.  li.,  p.  428. 

Dawson,  J.  W. :  Transactions  Roy.  Sac.  Edinburgh,  1916,  vol.  i.,  part  3  (No.  18), 

PP-  517-740- 
Russell,  J.  S.  R.:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910, 
p.  809. 

Syringomyelia. 

Nageotte,  J.,   AND  Riche,  A.:  Cornil   and  Ranvier,    Manuel  d'Hist.  Path., 

vol.  iii.,  1907. 
Starr,    M.A.:   Allbutt  and  Rolleston,   System   of  Medicine,  vol.  vii.,   1910, 

p.  852. 

Paralysis  Agitans, 

Hunt,  Ramsay:  Brain,  191 7,  vol.  xl.,  p.  58. 
Wilson,  S,  A.  K.:  Brain,  1914,  vol.  xxxvi.,  p.  427, 

Myasthenia  Gravis. 

Buzzard,  E.  F.:  Allbutt  and  Rolleston,  System  of  Medicine,  vol.  vii.,  1910. 

p.  50. 
Claude,  H.,  and  Porak,  R.:  L'enciphale,  1920.  p.  425. 


APPENDIX  I 
STAINING  METHODS 

Introductory. 

As  a  general  rule  celloidin  is  preferable  to  paraffin  for  imbedding 
and  cutting  tissues  of  the  nervous  system,  as  it  causes  less  shrinkage 
of  the  tissues  and  preserves  the  glial  structure  better.  Celloidin 
sections  are  also  easier  to  cut  and  to  handle  in  certain  special 
methods,  such  as  those  of  Marchi  and  Weigert-Pal.  On  the  other 
hand,  for  Nissl's  method,  especially  when  used  on  serial  sections, 
paraffin  sections  are  more  convenient.  Frozen  sections  are  necessary 
for  some  of  the  routine  methods,  and  may  be  used  for  all,  their  only 
disadvantage  being  their  fragility. 

It  is  not  proposed  to  give  here  an  account  of  all  the  methods 
wljich  have  been  and  may  be  applied  to  the  nervous  system,  and 
many,  especially  those  dependent  on  special  primary  fixation,  have 
been  omitted.  The  majority  of  the  methods  described  in  this  section 
are  those  which  are  used  as  a  routine  in  the  examination  of  nervous 
tissue.  It  is  not  always  necessary  nor  desirable  to  use  all  these 
methods  in  any  given  case,  but  for  the  full  examination  of  a  case  of 
rapidly  progressive  disease  it  is  necessary  to  stain  for  nerve  cells  by 
Nissl's  method  or  one  of  its  modifications ;  for  lipoids,  by  ScharlachR. 
or  Sudan  III;  for  neuro-fibrils,  by  theCajal  or  Bielschowsky  method ; 
for  myelin  sheaths,  both  by  Weigert-Pal  and  Marchi  methods ;  and 
for  neuroglial  cells  and  fibres,  by  tissue  stains,  such  as  haematoxylin 
and  van  Gieson. 

Fixation. 

Although  certain  special  methods  (notably  that  of  Cajal  for 
neurofibrils,  in  which  alcohol-ammonia  fixation  is  a  sine  qua  non, 
and  Nissl's  method  for  cells,  for  which  alcohol  is  the  best  fixative) 
demand  the  fixation  of  small  pieces  of  tissue  directly  in  a  special 
fluid,  as  a  general  rule  the  brain  and  cord  are  fixed  in  toto  in  lo  per 
cent.  formaHn  sahne,  which  is  changed  on  the  second  or  third  day. 
We  insist  on  the  addition  of  i  per  cent,  sodium  chloride  to  the 
formalin  solution,  as  it  not  only  helps  to  retain  the  original  size  and 
shape  of  the  tissues,  but  also  allows  the  formalin  to  penetrate  better. 
It  also  allows  the  first  sHces  across  the  brain  to  be  made  at  the  end 

305  •  20 


3o6  STAINING  METHODS 

of  five  to  seven  days  without  any  resulting  deformity  of  the  brain, 
which  is  of  great  advantage  for  early  diagnosis.     When  this  is  done 
the  brain  fixes  more  rapidly  and  completely,  and  will  usually  be 
found  to  be  completely  fixed  at  the  end  of  a  fortnight.     For  the 
fixation  of  a  whole  brain,  four  litres  of  formalin  saline  are  necessary, 
and  the  pot  used  should  have  a  lid  which  fits  sufficiently  well  to 
prevent  the  formalin  evaporating  out  of  the  fluid,  and  handles  at 
either  side,  to  which  a  string  can  be  tied  which  passes  under  the 
basilar  artery  and  suspends  the  brain  in  the  fluid.    At  the  end -of  a 
week  it  is  possible  to  select  pieces  for  examination    by   special 
methods.     It  is  often  convenient  to  run  a  horsehair  through  these, 
so  that  they  are  retained  in  their  proper  order  in  their  passage 
through  the  various  fluids.     Those  for  the  VVeigert-Pal  and  Marchi 
methods   are  then   put   directly  into  Muller's  fluid,  or  Weigert's 
primary  mordant,  while  those  for  freezing  and  for  Nissl  and  tissue 
staining  are  either  fixed    for   two   days    further   in    formalin   or 
preferably  in  Zenker's  fluid  for  twelve  to  twenty-four  hours.      In 
either  case   they  are   washed   for  twenty-four   hours   in   running 
water  before  anything  further  is  done. 

Imbedding  in  Celloidin. 

After  washing  in  water,  pieces  up  to  5  mm.  in  thickness  are  passed 
through  increasing  strengths  of  alcohol  up  to  absolute  alcohol,  in 
which  they  remain  for  twenty-four  to  forty-eight  hours.     They  are 
then  transferred  for  a  similar  time  to  equal  parts  of  alcohol  and 
ether,  and  from  this  passed  into  a  thin  solution  of  celloidin  in  alcohol 
and  ether  (which  should  be  so  thin  as  to  give  only  a  slight  indication 
of  viscosity  when  it  is  shaken  about  in  the  bottle).     After  remaining 
in  this  for  at  least  a  week,  they  are  changed  into  thicker  celloidin 
(about  6  per  cent.).     In  this  they  remain  any  time  from  four  days 
to  a  fortnight.     They  are  then  placed  in  order  in  a  shallow  flat- 
bottomed  glass  vessel,  such  as  an  evaporating  basin,  the  side  from 
which  the  first  sections  are  to  be  taken  being  uppermost.   Celloidin  as 
thick  and  viscid  as  possible  is  then  poured  on  to  cover  them .   The  dish 
is  covered  completely  for  the  first  day  in  order  to  allow  of  the  escape 
of  any  bubbles  of  air,  and  then  the  cover  is  raised  shghtly  the  second 
dav,  and  almost  completely  thereafter  until  the  celloidin  is  so  firm 
that  the  pressure  of  the  finger  makes  no  impression  on  it.     The 
celloidin  is  then  removed  entire  from  the  dish,  by  cutting  round  the 
edges,  and  trimmed  into  small  pieces  containing  the  blocks  of  tissue. 
These  are  then  mounted  on  hard  wood  blocks  by  means  of  6  per  cent, 
celloidin,  the  side  of  the  tissue  which  was  next  the  glass  resting  on  the 


TISSUE  STAINS  307 

wood.  Cheap  and  excellent  blocks  are  made  from  elm  or  oak,  which 
has  been  soaked  in  methylated  spirit  to  rid  it  of  resin,  and  cut  to  the 
required  shape.  Smoother  woods,  such  as  birch  or  sycamore,  afford 
less  grip  for  the  celloidin,  but  can  be  used  if  shallow  saw  cuts  are 
made  across  the  surface  on  which  the  blocks  rest.  After  the  tissue 
is  mounted  on  the  blocks  they  are  named  and  numbered  with  Chinese 
ink,  and  when  the  celloidin  is  dry  are  stored  in  spirit  in  large-mouthed 
bottles  for  at  least  twenty-four  hours  before  cutting.  Wooden 
blocks  with  tissue  mounted  on  them  can  be  kept  in  50  to  60  per  cent, 
alcoholfor  an  indefinite  time,  and  it  is  always  preferable  to  keep 
them  in  this  way  until  they  are  finished  with. 

A. — General  Tissue  Stains. 

Haematoxylin  and  van  Gieson. 

Overstain  sections,  either  frozen,  paraffin,  or  celloidin,  in  any  good 
haematoxylin  mixture.  Mayer's  haemalum,  Delafield's  alum 
haematoxylin  and  Weigert's  iron  haematoxylin  are  to  be  recom- 
mended. Decolourise  with  acid  alcohol,  not  so  completely  as  for 
the  eosin  counterstain.     Wash  thoroughly  in  tap  water. 

Stain  for  eight  to  twelve  seconds  in  van  Gieson 's  mixture,  which 
should  be  prepared  from  the  stock  solutions  within  a  few  days  of  use. 

Van  Gieson 's  stain: 

Sol.  A. — Acid  fuchsin  . .         . .         . .         . .         i  gramme. 

0*6  per  cent.  sol.  of  picric  acid  in 

distilled  water      . .         . .         . .    100  c.c. 

Sol.  B. — Sat.  sol.  (o'6  per  cent.)  picric  acid  in  distilled  water. 

For  use  take  i  part  of  A  and  9  parts  of  B. 

Wash  rapidly  in  distilled  water  or  in  tap  water,  to  which  a  few 
drops  of  acetic  acid  have  been  added  to  render  it  acid. 

Transfer  for  a  few  seconds  to  95  per  cent,  alcohol. 

Paraffin  and  frozen  sections  are  then  transferred  to  absolute 
alcohol  and  xylol,  celloidin  sections  to  carbol-xylol  (phenol 
crystals  i,  xylol  3),  and  when  clear  to  xylol.  It  has  been  recom- 
mended that  the  xylol  should  be  acidified  either  by  saturation  with 
salicylic  acid  or  with  acetic  acid  (2  drops  for  each  100  c.c.) :  this  is 
not  necessary  if  the  xylol  is  neutral. 

Mount  in  Canada  balsam  which  has  been  saturated  with  salicylic 
acid.  This  is  absolutely  necessary  if  the  sections  are  to  retain  their 
pink  staining,  and  its  omission  has  been  responsible  in  the  past  for 
the  unpopularity  of  this  stain.  By  this  method  fibrous  tissue  is 
stained  red,  elastic  tissue  and  red  blood  corpuscles  yello.w,  and 
muscular  and  nervous  tissue  brownish  or  terra-cotta. 


3o8  STAINING  METHODS 

B. — Nissl  Granules. 

The  best  fixative  for  Nissl  granules  is  95  per  cent,  alcohol  for 
three  to  five  days,  changed  every  day.  Only  thin  pieces  of  brain 
should  be  fixed  in  this  way,  but  the  cord  can,  if  desired,  be  fixed 
entire.  In  most  cases,  however,  this  is  not  desirable,  as  fixation 
with  alcohol  prevents  any  study  of  degeneration  in  the  myelin 
sheaths.  Formalin  or  any  of  the  corrosive  sublimate  fixatives  (e.g. 
Zenker's  or  Dominici's  fluids)  may  also  be  used,  in  which  case  the 
pieces  must  be  washed  for  at  least  twenty-four  hours  in  running 
water  after  fixation.  Sections  may  be  made  by  the  freezing,  paraffin 
or  celloidin  methods.  Nissl  attached  pieces  of  alcohol-fixed  tissue 
to  blocks  of  wood  by  means  of  gum  arabic,  and  cut  them  as  if  they 
had  been  celloidin  blocks.  Celloidin  sections  are  most  easily  and 
satisfactorily  stained  after  removal  of  the  celloidin  by  placing  them 
in  alcohol  and  ether  for  twelve  to  twenty- four  hours.  They  are 
transferred  through  absolute  and  80  per  cent,  alcohols  to  distilled 
water  before  being  stained.  Paraffin  sections  are  treated  by  the 
usual  method  for  removing  paraffin  and  placed  in  distilled  water. 

Stain  with  either  polychrome  methylene  blue,  i  per  cent,  toluidin 
blue,  or  2  per  cent,  thionin  blue,  for  twenty  to  thirty  minutes  in  the 
paraffin  oven  from  50°  to  55°  C,  or  stain  in  Nissl's  methylene 
blue-soap  solution,  which  has  been  allowed  to  ripen  for  at  least 
three  months. 

Methylene  blue      . .  . .         . .         •  •     375  grammes. 

Venetian  soap  shavings     ..         ..         ..     175  grammes. 

Distilled  water        . .  . .  . .  . .  1,000  c.c. 

Shake  well. 

The  sections  are  stained  in  this  solution  by  heating  the  stain  rapidly 
over  a  fiailie  until  bubbles  rise. 

Wash  rapidly  in  water. 

Differentiate  first  in  90  per  cent,  alcohol.  If  the  sections  are 
deep  blue  in  colour  after  the  first  few  minutes  in  this,  they  may  be 
differentiated  more  rapidly  by  either  of  the  following  solutions : 

1 .  Anilin  oil  (colourless) 
Alcohol,  95  per  cent,  or  absolute  . . 

2.  Gothard's  solution: 

Creosote  (pure  beechwood)     . . 
Cajuput  oil 

Xylol 

Absolute  alcohol 


10 

c.c, 

90 

c.c, 

50 

c.c, 

40 

c.c, 

50 

c.c. 

50 

c.c 

NISSL  GRANULES  309 

In  either  case  the  differentiation  should  only  be  continued  until 
the  nerve  cells  stand  out  plainly  from  the  surrounding  tissue. 
Continue  the  differentiation  with  absolute  alcohol  until  the  Nissl 
granules  stand  out  clearly  from  the  rest  of  the  nerve  cell,  which, 
with  the  exception  of  the  nucleolus,  should  be  almost  or  completely 
colourless.  This  process  is  best  watched  under  the  microscope 
after  transferring  the  sections  ternporarily  to  xylol.  The  differentia- 
tion need  not  be  carried  far  enough  to  decolourise  the  nuclei  of  the 
glial  or  connective-tissue  cells,  or  of  the  smallest  nerve  cells. 

Wash  for  about  fifteen  minutes  in  xylol.  Place  on  slides,  blot 
and  mount  with  a  coverslip  by  means  of  pure  cedar- wood  oil.  The 
slides  are  then  put  into  the  incubator  at  37°  C.  for  twenty-four  hours, 
after  which  the  cedar-wood  oil  will  have  set  firmly. 

It  is  possible  to  use  Canada  balsam  if  this  is  neutralised  by  satura- 
tion with  lithium  carbonate.  It  offers  no  advantages  over  cedar- 
wood  oil,  in  which  the  sections  should  remain  for  years  without 
losing  their  colour. 

If  it  is  necessary  to  keep  the  celloidin  in  the  sections  during  the 
whole  of  the  process,  the  following  variations  in  the  technique  must 
be  made.  The  sections  should  be  thin,  not  more  than  8  {jL. 
After  staining  they  are  transferred  to  95  per  cent,  alcohol;  then,  if 
necessary,  to  anilin  oil — alcohol  made  up  with  95  per  cent,  alcohol 
and  returned  for  final  differentiation  to  fresh  95  per  cent,  alcohol. 
They  are  then  cleared  with  cajuput  or  origanum  oil,  washed  in  xylol, 
and  mounted  as  already  described.  Only  the  purest  celloidin  can 
be  used  for  this  purpose,  and  even  this  will  be  found  to  retain  the 
stain  to  some  extent. 

Rosin's  Method  for  Nissl  Bodies. 

Rosin's  method  will  be  found  useful,  both  for  micro-photography 
and  where  it  is  wished  to  counterstain  preparations  in  which  the 
myelin  sheaths  have  been  stained  black.  He  uses  saturated  watery 
solution  of  neutral  red  in  place  of  basic  blue  solution.  Differentia- 
tion is  done  rapidly  with  alcohol  alone,  and  sections  are  mounted  as 
before. 

C— Neuro-Fibrils. 

Ramon-y-CajaVs  Method. 
Fix  small  pieces  of  tissue  for  twenty-four  to  forty-eight  hours  in : 

96  per  cent,  alcohol       . .  . .  . .  . .  100  c.c. 

Ammonia  -880    . .         . .         . .         . .         . .        0-25  c.c. 


310  STAINING  METHODS 

Wash  rapidly  in  distilled  water,  and  transfer  to  3  per  cent,  silver 
nitrate  solution  for  five  to  six  days  in  the  incubator  at  37°  C. 

Wash  rapidly  in  distilled  water. 

Reduce  in  the  following  mixture  for  twenty-four  hours  in  the  dark 
at  room  temperature  (two  stock  solutions  are  prepared  and  kept 
separately) : 


Sol.  A. — Sod.  sulphite 
Formol 
Distilled  water 

Sol.  B. — Pyrogallic  acid 
Distilled  water 


5  grammes. 
50  c.c. 
200  c.c. 

20  grammes. 
800  c.c. 


For  use  take  25  c.c.  of  A  and  80  c.c.  of  B. 

Wash  for  a  few  minutes  in  distilled  water  and  imbed  in  paraffin 
or  celloidin.     Cut  thin  sections. 

After  the  sections  have  been  passed  into  distilled  water  they  are 
placed  in  a  combined  toning  and  fixing  bath,  where  they  remain 
for  a  few  minutes  until  they  become  of  a  grey- violet  colour. 

Toning  and  fixing  bath: 

Ammon.  sulpho-cyanide      . .  . .  . .         3  grammes. 

Sod.  thiosulphate      . .  . .  . .  . .         3  grammes. 

Distilled  water  to 100  c.c. 

Add  just  before  use  a  few  drops  of  i  per  cent,  gold  chloride. 
Wash,  dehydrate,  clear,  and  mount  in  Canada  balsam. 

Bielschow sky's  Method  {Modified  by  Da  Fano). 

Fix  small  pieces  of  nervous  tissue  for  at  least  eight  days  in  20  per 
cent,  formol  (which  should  not  be  acid). 

Cut  at  15  to  20  //  on  the  freezing  microtome- 
After  washing  in  distilled  water  for  one  or  more  hours  the  sections 
are  transferred  to  a  mixture  of  equal  parts  of  20  per  cent,  formol, 
and  of  either  methyl  alcohol  or  pyridin  for  twenty-four  hours. 

Wash  for  six  to  twenty-four  hours  in  several  changes  of  distilled 
water. 

Put  into  2  per  cent,  silver  nitrate  solution  for  twenty-four  hours 
in  the  incubator  at  37°  C. 

Wash  for  a  few  seconds  only  in  distilled  water,  and  transfer  to 
Bielschowsky's  solution  made  up  as  follows : 

To  5  c.c.  of  20  per  cent,  silver  nitrate  solution,  in  a  clean  50  c.c. 
cylindrical  measure,  add  2  drops  of  40  per  cent.  NaOH.  A  heavy 
brown  precipitate  is  formed.  (It  is  sometimes  preferable  to  wash 
this  with  distilled  water  once  or  twice,  allowing  it  to  settle  and 


NEURO-FIBRILS  S" 

pipetting  off  the  top  fluid  before  proceeding.  In  any  case,  care 
must  be  taken  that  the  powdery  white  substance  which  tends  to 
gather  round  the  neck  of  the  bottle  of  caustic  soda  is  washed  off  with 
distilled  water  before  it  is  used.)  Then  dissolve  up  the  precipitate 
of  silver  hydroxide  with  strong  ammonia,  adding  only  just  enough 
ammonia  to  dissolve  the  precipitate  with  thorough  stirring.  Dilute 
to  40  c.c. 

This  solution  should  be  perfectly  colourless. 

In  this  the  sections  remain  for  thirty  minutes. 

Wash  rapidly,  for  a  few  seconds  only,  in  two  changes  of  distilled 
water.  This  washing  is  absolutely  necessary,  but  reduces  the 
intensity  of  the  staining  considerably  if  at  all  prolonged.  It  also 
takes  the  silver  stain  out  of  the  fibrous  tissue,  and  must  be  prolonged 
to  half  to  one  minute  when  staining  the  peripheral  nerves,  in  order 
to  differentiate  the  neuro-fibrils  from  the  surrounding  tissue.  The 
resulting  decolourisation  may  be  compensated  for  by  leaving  the 
sections  in  2  per  cent,  silver  nitrate  for  a  longer  time. 

Transfer  to  20  per  cent,  formol  made  up  with  tap  water,  and  leave 
in  this  for  two  to  twenty-four  hours,  changing  after  the  first  few 
minutes. 

Wash  thoroughly  in  distilled  water,  and  "  tone  "  in  a  very  weak 
solution  of  gold  chloride  (10  drops  of  i  per  cent,  gold  chloride  solution 
to  25  c.c.  of  distilled  water). 

"  Fix  "  in  sodium  thiosulphate  (5  per  cent,  watery  solution)  for 
about  five  minutes.  Wash  in  distilled  water  for  at  least  twenty 
minutes,  dehydrate,  and  mount  in  Canada  balsam. 

All  glassware  used  for  this  method  must  be  perfectly  clean  and 
washed  out  with  alcohol,  flamed,  and  finally  washed  with  distilled 
water  before  use.  The  distilled  water  must  be  fresh  and  neutral. 
Da  Fano  recommends  that  it  should  be  doubly  distilled  over 
potassium  permanganate. 

The  sections  should  only  be  handled  with  glass  rods  drawn  out 
fine  and  bent  at  the  tip  in  the  Bunsen  burner.  If  these  precautions 
are  observed,  it  is  possible  to  get  uniformly  good  results  with  the 
above  method  with  most  forms  of  nervous  tissue. 


Bielschow sky's  Method  for  Blocks  of  Tissiie. 

This  method  cannot  be  relied  on  to  show  the  fine  intracellular 
neuro-fibrils,  and  it  is  not  possible  in  using  it  to  differentiate  the 
neuro-fibrils  from  the  neighbouring  fibrous  tissue.  It  is,  however, 
of  value  in  examining  tissue  the  consistence  of  which  does  not  allow 
of  frozen  sections,  e.g.  softenings  of  the  brain  or  cord,  and  soft 


312  STAINING  METHODS 

tumours,  when  the  condition  of  the  axis  cyHnders  and  dendrites  is 
all  that  is  in  question. 

Fix  small  pieces  of  tissue,  as  thin  as  possible,  in  20  per  cent,  formol 
for  at  least  eight  days. 

Wash  for  a  few  hours  in  running  water. 

Place  in  pure  pyridin  for  twenty-four  hours. 

Wash  for  twenty-four  hours  in  running  water,  and  then  for  a  few 
hours  in  several  changes  of  distilled  water. 

Put  into  3  per  cent,  silver  nitrate  solution  in  the  dark  for  four  to 
five  days  (or  for  two  to  three  days  in  the  incubator  at  37°  C). 

Wash  rapidly  in  distilled  water. 

Place  in  Bielschowsky's  solution,  made  up  as  already  described, 
for  four  to  five  hours. 

Wash  rapidly  in  two  changes  of  distilled  water,  and  transfer  to 
20  per  cent,  formol  for  twelve  hours. 

Wash  in  distilled  water,  dehydrate,  clear,  and  imbed  in  paraffin 
in  the  usual  way.  Cut  thin  sections.  Tone,  fix,  clear,  and  mount 
as  described  for  preparations  by  Cajal's  method. 

D. — Myelin. 

Weigeri's  Method. 

Fix  in  formol  saline  one  week. 

Put  pieces  up  to  i  cm.  in  thickness  into  Muller's  fluid  for  six  to 
eight  weeks.  The  mordanting  process  may  be  hastened  by  putting 
the  bottle  containing  the  pieces  in  Muller's  fluid  in  the  incubator 
3-t  37°  C.  It  is  necessary  to  change  the  fluid  as  soon  as  it  shows  the 
slightest  turbidity. 

Alternatively  the  mordanting  process  may  be  greatly  shortened 
by  using  Weigert's  primary  mordant,  in  which  the  pieces  should 
remain  for  seven  to  fifteen  days  according  to  their  thickness. 

(Weigert's  primary  mordant: 

Potassium  bichromate        5  grammes. 

Fluorchrome  ..  ..  ..  ..2-5  grammes. 

Water  100  c.c. 

Boil  the  bichromate  and  add  the  fluorchrome  while  boihng,  cool, 
and  filter.) 

Wash  in  running  water. 

Pass  through  increasing  strengths  of  alcohol  into  alcohol  and 
ether. 

Imbed  in  celloidin. 

Cut  at  15  to  20  jLi. 


MYELIN  SHEATHS  313 

Prepare  some  clean  glass  plates,  e.g.  J-plate  or  J-plate  negatives 
from  which  the  gelatin  has  been  removed,  and  coat  these  thinly 
with  Obregia's  solution,  which  is  allowed  to  dry. 

Obregia's  solution : 


Syrupus  simplex 
Dextrin  syrup 
Alcohol,  95  per  cent. 


30  CO. 
20  c.c. 
20  c.c. 


The  sections  are  received  directly  after  being  cut  in  methylated 
spirit,  and  are  transferred  from  this  on  to  the  plates  in  order.  They 
may  be  arranged  exactly  as  they  will  be  mounted  up,  or  in  serial 
order.  For  routine  work  it  is  often  of  advantage  to  mount  up  one 
section  from  each  block  in  order  from  the  medulla  to  the  sacral 
end  of  the  cord.  After  they  are  carefully  arranged,  they  are 
blotted  firmly,  and  a  very  thin  film  of  thin  celloidin  is  poured  on  to 
them.  This  is  allowed  to  dry  partially  in  the  air  for  about  five 
minutes,  and  the  plate  is  then  put  in  methylated  spirit  to  allow  the 
celloidin  film  to  harden.  It  is  then  transferred  to  a  dish  of  warm 
water,  which  dissolves  the  gummy  solution  and  allows  the  film 
of  celloidin  containing  the  sections  imbedded  in  it  to  float  off.  This 
film  is  then  treated  as  a  large  celloidin  section  and  is  stained, 
differentiated,  and  mounted  up,  either  whole  or  after  being  cut  into 
convenient  sizes. 

(From  this  stage  the  films  may  be  stained  either  by  the  Weigert 
or  the  Kultschitsky-Pal  method  [v.  inf.]). 

Place  in  Weigert 's  secondary  mordant  ("  gliabeize,"  p.  317)  in  the 
incubator  at  37°  C.  for  twenty-four  hours. 

Wash  in  water. 

Stain  in  Weigert 's  iron  haematoxylin,  made  by  mixing  equal 
volumes  of  the  following  solutions  A  and  B.  Stain  for  twenty-four 
hours. 

Sol.  A. — Haematoxylin         ..  ..  ..         i  gramme. 

Absolute  alcohol     . .  . .  . .     100  c.c. 

(Ripen  in  the  sun  for  two  to  four  weeks.) 

Sol.  B. — Liq.  ferri  perchlor.  .  .  .  .  .  .         4  c.c. 

Pure  hydrochloric  acid       .  .  .  .         i  c.c. 

Distilled  water  to  100  c.c. 

Wash  in  several  changes  of  water. 
Differentiate  in: 

Borax  . .  . .  . .  . .  . .  2  grammes. 

Pot.  ferricyanide      ..  ..  ..  ..       2-5  grammes. 

Distilled  water        . .         . .         . .         . .      100  c.c. 


314  STAINING  METHODS 

Renew  the  differentiator  several  times,  continuing  the  differentia- 
tion until  the  myehnated  fibres  stand  out  dark  blue  or  black  against  a 
yellowish  background. 

Wash  for  twenty-four  hours.  Dehydrate  in  increasing  strengths 
of  alcohol  up  to  95  per  cent.  Clear  in  carbol-xylol.  Wash  in  xylol. 
Mount  in  Canada  balsam. 

KuUschitsky-Pal  Method. 

Mordant,  imbed,  cut  and  plate  as  for  Weigert's  method. 

Transfer  the  films  for  half  an  hour  to  a  half-saturated  solution  of 
copper  acetate  in  distilled  water. 

Stain  in  Kultschitsky's  haematoxylin  in  the  incubator  at  37°  C. 
for  twenty-four  to  forty-eight  hours. 

(Kultschitsky's  haematoxylin : 

Ripened  10  per  cent.  alcohoHc  solution  of  haema- 
toxylin      . .          . .          . .          . .          . .          . .  10  c.c. 

Glacial  acetic  acid     ..          ..          ..          ..          ..  2  c.c. 

Distilled  water          90  c.c.) 

Transfer  directly  to  Muller's  fluid  for  five  to  fifteen  minutes. 

Differentiate  by  Pal's  method: 

Transfer  the  films  for  quarter  to  half  a  minute  to  0-25  per  cent, 
potassium  permanganate.  Wash  in  tap  water.  Transfer  for  a 
similar  time  to  Pal's  solution.  Wash  again.  Transfer  again  to 
permanganate,  and  repeat  until  the  myehnated  fibres  stand  out 
blue-black  against  a  colourless  background. 

Pal's  solution: 

Oxalic  acid        . .  . .  . .  . .  . .      0-5  grammes. 

Sod.  sulphite 0-5  grammes. 

Distilled  water  . .  . .  . .  . .     100  c.c. 

Wash  for  several  hours  in  tap  water,  adding  at  first  a  few  drops 
of  lithium  carbonate  solution  to  give  a  blue  colour  to  the  sections. 
Dehydrate  and  mount  as  in  Weigert's  method. 

Lithium  carmine  or  Van  Gieson's  stain  may  be  used  as  a  counter- 
stain. 

Weigert's  Method  applied  to  Frozen  Sections. 

This  method  gives  very  good  and  constant  results,  and  has  the 
advantage  of  greatly  reducing  the  time  needed  for  diagnosis.  It 
also  has  the  advantage  that  it  allows  of  similar  sections  being 
examined  by  Nissl's,  Bielschowsky's,  and  W^eigert's  methods,  as 
well  as  by  Marchi's  or  other  stains  for  myelin  degeneration.  Its 
disadvantages  are  those  common  to  all  frozen  sections,  e.g.  loss  of 
meninges  and  nerve  roots,  and  difficulty  in  cutting  serial  sections. 


MYELIN  DEGENERATION  315 

After  formalin  fixation,  cut  on  the  freezing  microtome  at  20  to 

30/^- 

Put  sections  into  MuUer's  fluid  for  five  to  seven  days  in  the 
incubator  at  37°  C,  or  into  Weigert's  primary  mordant  for  two  to 
three  days  in  the  incubator. 

Plate  with  celloidin  on  gummed  plates,  as  described  for  celloidin 
sections.  This  step  may  be  taken  before  mordanting  in  the  chrome 
solutions  if  alcohol  not  stronger  than  75  per  cent,  is  used. 

Stain,  differentiate,  and  mount  as  for  celloidin  sections. 

Marchi*s  Method  for  Degeneration. 

After  fixation  in  formol-saline,  mordant  thin  pieces  of  brain  and 
spinal  cord,  not  more  than  3  mm.  in  thickness,  in  Muller's  fluid, 
for  two  to  three  weeks  according  to  the  size  and  thickness  of  the 
pieces.  The  fluid  should  be  changed  as  soon  as  it  shows  any  signs 
of  turbidity. 

Without  washing,  pass  into  Marchi's  fluid  in  a  well-stoppered 
bottle,  taking  care  that  the  pieces  do  not  rest  directly  on  the  bottom 
or  on  one  another.  This  can  be  avoided  by  stringing  the  pieces  on 
a  horsehair.  The  pieces  remain  in  this  fluid  for  two  to  four  weeks, 
according  to  the  temperature  of  the  laboratory  and  the  size  of  the 
pieces.  A  few  c.c.  of  i  per  cent,  osmic  acid  are  added  once  or  twice 
every  week,  or  as  soon  as  the  fluid  ceases  to  smell  strongly  of  osmic 
acid. 

Marchi's  fluid: 

Muller's  fluid  . .         . .         . .         . .         . .     2  parts. 

I  per  cent,  osmic  acid       . .  . .  . .  . .     i  part. 

Add  just  before  use  i  drop  of  acetic  acid  for  every  20  c.c.  of 
Marchi's  fluid. 

Wash  for  twelve  to  twenty-four  hours  in  running  water. 

Dehydrate  rapidly  and  imbed  in  celloidin  or  paraflin. 

Cut  at  15  to  30  ju.  Transfer  to  spirit  and  thence  to  95  per 
cent,  alcohol.  Clear  in  carbol-xylol ;  mount  in  chloroform  balsam, 
preferably  without  a  coverslip,  which  may  be  easily  done  by  blotting 
the  sections  on  a  slide,  covering  with  a  drop  of  cTiloroform  balsam 
and  putting  them  in  the  incubator  at  37°  C.  overnight.  Another 
drop  of  balsam  may  be  added  next  day  if  it  is  thought  necessary. 

Busch's  Modification  of  Marchi's  Method. 
Fix  and  mordant  small  pieces  up  to  5  mm.  thick,  as  in  Marchi's 
method. 

Wash  for  twelve  to  twenty-four  hours  in  running  water. 


3i6  STAINING  METHODS 

Put  in  Busch's  fluid  in  a  well-stoppered  bottle  with  the  same 
precautions  as  in  Marchi's  method.  Leave  for  eight  to  fourteen  days, 
preferably  in  the  incubator,  at  37°  C. 

Busch's  fluid: 

I  per  cent,  osmic  acid      . .  .  •  •  •  . .     i  part. 

1-5  per  cent,  sodium  iodate         . .  . .  . .     2  parts. 

Wash,  imbed,  cut,  and  mount  as  in  Marchi's  method. 

In  this  method  the  ground  substance  is  less  stained  than  in  the 
original  Marchi  method,  and  the  osmic  acid  penetrates  better.  It 
is,  therefore,  more  suitable  for  fairly  wide  sections,  as  in  studying 
the  tract  degenerations  in  the  human  brain  and  brain-stem,  and  for 
photographic  reproduction.  On  the  other  hand,  it  is  perhaps  not 
quite  so  accurate  as  the  Marchi  method,  and  sometimes  black  dots 
are  found  in  sections  stained  in  this  way  which  are  not  due  to  fat. 
These  will  usually  be  avoided  if  the  pieces  are  washed  thoroughly 
between  Muller's  and  Busch's  fluids. 

Marchi's  method  or  its  modifications  can  easily  be  appHed  to 
frozen  sections,  which  are  most  conveniently  cut  after  fixation  in 
formahn.  In  this  case  the  individual  steps  are  the  same,  but  the 
time  required  for  each  can  be  considerably  reduced. 

E.— Fat. 

Osmic  Acid. 

This  is  used  in  the  Marchi  method,  where  the  primary  mordanting 
with  Muller's  fluid  prevents  the  osmic  acid  from  staining  the  normal 
myelin. 

When  it  is  desired  to  stain  all  the  lipoid  substances  in  nervous 
tissue,  e.g.  in  peripheral  nerves,  the  tissues  may  be  fixed  in  formol, 
and  after  washing  in  water  cut  on  the  freezing  microtome.  The 
sections  are  then  stained  for  twenty-four  hours  in  i  per  cent,  osmic 
acid,  counterstained  in  alum  carmine  or  neutral  red,  if  desired, 
washed  for  several  hours  in  80  per  cent,  alcohol,  and  mounted  in 
Kaiser's  glycerin  gelatin.  Or  they  may  be  mounted  in  benzene 
balsam,  after  being  passed  rapidly  through  absolute  alcohol  and 
benzene.  In  this  case  it  is  better  not  to  use  a  coverslip,  but  to  let 
the  balsam  dry  on  the  sections. 

Sudan  III  and  Scharlach  R. 
These  stains  are  particularly  valuable  for  staining  sections  of 
the  central  nervous  system.     They  stain  myelin  and  intracellular 
lipochromes,  but  not  so  deeply  as  degenerated  myelin  and  other 


SCHARLACH  R.  317 

neutral  fats.  They  are,  however,  of  little  value  for  studying  the 
paths  of  degenerated  fibres. 

After  formalin  fixation,  cut  sections  as  thin  as  possible  on  the 
freezing  microtome. 

Pass  into  70  per  cent,  alcohol  for  a  few  minutes. 

Stain  for  two  or  three  minutes  in  a  covered  vessel  in  a  solution  of 
Scharlach  R.  made  by  saturating  a  mixture  of  equal  parts  of 
70  per  cent,  alcohol  and  of  acetone  with  the  dye,  filtering  or  decanting 
the  clear  fluid  immediately  before  use. 

Or  stain  in  a  saturated  solution  of  Sudan  III  in  70  to  80  per  cent, 
alcohol  for  fifteen  to  twenty  minutes. 

Wash  for  a^few  seconds  in  70  per  cent,  alcohol,  and  transfer  to 
water. 

Counterstain  for  a  minute  or  two  in  alum-haematoxylin,  dif- 
ferentiating rapidly  in  acid  alcohol  (made  up  with  70  per  cent, 
alcohol)  if  necessary. 

Wash  thoroughly  in  water.  A  few  drops  of  ammonia  or  of  a 
saturated  solution  of  lithimn  carbonate  in  the  water  brings  up  the 
blue  colour  of  the  haematoxylin  more  rapidly. 

Mount  in  glycerin  gelatin. 

Kaiser's  glycerin  gelatin : 

Finest  French  gelatin        ., 40  grammes. 

Water           210  c.c. 

Glycerin        . .         . .         . .         . .         . .  250  c.c. 

Carbolic  acid  crystals        5  grammes. 

Soak  the  gelatin  in  the  water  for  two  hours.  Add  the  glycerin 
and  carbolic  acid  and  warm  for  two  to  fifteen  minutes,  stirring  all 
the  time  until  the  mixture  is  smooth.  Filter  through  filter  paper 
in  the  paraffin  oven  at  50°  to  55°  C. 

F. — Neuroglia. 

Weigert's  Method. 

Small  pieces  of  nervous  tissue  taken  at  the  autopsy  within  a  few 
hours  of  death  are  placed  directly  in  Weigert's  "gliabeize." 

"Gliabeize":  Dissolve  2-5  grammes  of  fluorchrome  (CrFg)  in 
100  c.c.  of  distilled  water.  Add,  while  boiling,  5  c.c.  of  36  per  cent, 
acetic  acid  and  5  grammes  of  neutral  copper  acetate.  Cool  and 
add  10  c.c.  of  formol. 

The  pieces  of  tissue  remain  in  this  for  eight  days  or  more. 

Wash  rapidly  and  imbed  in  celloidin. 

Place  sections  in  0-3  per  cent,  solution  of  potassium  permanganate 
for  ten  minutes. 


3i8  STAINING  METHODS 

Wash  thoroughly. 

Place  for  two  to  four  hours  in  the  following  mixture,  made  by 
adding  90  c.c.  of  A  to  10  c.c.  of  B.- 
Sol. A. — Chromogen  5  grammes. 

Formic  acid,  sp.  gr.  1-2     . .  . .         5  c.c. 

Distilled  water     . .  . .  . .     100  c.c. 

Sol.  B. — Sod.  hyposulphite  (thiosulphate)        10  grammes. 
Distilled  water     . .  . .  . .      100  c.c. 

Wash  rapidly  in  water. 

Place  in  5  per  cent,  solution  of  chromogen  (carefully  filtered)  for 
ten  to  twelve  hours. 

Wash  in  water. 

Place  sections  on  a  clean  slide,  dry  with  filter  paper,  and  stain  for 
half  to  one  minute  in  the  following  stain: 

70  to  80  per  cent,  alcohol  saturated  with  methyl 

violet  by  heating  . .  . .  . .  . .     100  c.c. 

5  per  cent,  aqueous  solution  of  oxalic  acid         . .         5  c.c. 

Remove  the  excess  of  stain,  blot  with  filter  paper,  put  on  a  few 
drops  of  concentrated  Gram's  iodine  (iodine  i,  potassium  iodide  2, 
water  100)  for  about  thirty  seconds. 

Dry  again  with  filter  paper. 

Decolourise  with  a  mixture  of  equal  parts  of  xylol  and  pure 
anilin  oil. 

Wash  thoroughly  in  xylol.     Mount  in  Canada  balsam. 

This  method  sometimes  gives  remarkably  fine  results,  but  is  not 
to  be  relied  on  to  give  good  results  in  all  cases.  The  length  of  time 
between  the  death  of  the  patient  and  the  autopsy  seems  to  play  a 
more  than  usually  important  part  in  the  success  or  otherwise  of  the 
method,  and  sometimes  the  tissues  do  not  stain  well  for  no  ascer- 
tainable reason.  The  method  is  not  apphcable  to  the  tissues  of 
the  lower  animals,  for  which  Cajal's  silver  method,  after  fixation  in 
formol-ammonium  bromide,  is  the  best  (p.  320). 

It  is  allowable  to  fix  the  tissues  first  in  10  per  cent,  formol  for 
not  more  than  twenty-four  hours. 

Lhermitte's  Method. 

Fix  for  at  least  fourteen  days  in  10  per  cent,  formol.  If  the  brain 
is  fixed  in  toto  in  formalin,  sections  should  be  made  through  it  on 
the  day  after  the  autopsy  to  allow  of  more  rapid  fixation.  It  is 
best  at  this  stage  to  take  out  the  pieces  on  which  the  method  is 


NEUROGLIA  STAINS  319 

to  be  performed  and  fix  them  in  fresh  formol,  which  should  be 
renewed  several  times. 

Cut  frozen  sections,  not  too  thin. 

The  sections  after  washing  are  refixed  and  mordanted  in  the 
following  solution: 

Chromic  acid,  i  per  cent.    . .          . .          . .          • .  50  c.c. 

Osmic  acid,  i  per  cent.       . .          . .          . .          . .  12  c.c. 

Acetic  acid,  2  per  cent.       . .          . .          . .          . .  8  c.c. 

Distilled  water          30  c.c. 

The  sections  remain  in  this  for  twenty-four  to  forty-eight  hours. 

Wash  rapidly  in  water  and  spread  the  sections,  one  by  one,  on 
glass  shdes,  which  are  covered  with  pieces  of  cigarette  paper.  This 
remains  fixed  to  the  slide  in  water,  and  the  sections  remain  on  it 
more  firmly  than  on  the  slide  itself.  Further,  it  allows  the  stain 
to  penetrate  better. 

Stain  in  1-5  per  cent,  solution  of  Victoria  blue  in  distilled  water, 
heating  the  slide  carefully  several  times  as  in  Ziehl-Neelsen  staining. 
Pour  off  the  excess  of  stain  and  add  a  few  drops  of  concentrated 
Gram's  solution  (iodine  i,  potassium  iodide  2,  water  200).  Allow 
to  act  for  one  minute. 

Pour  this  off  and  put  on  directly  equal  parts  of  pure  anilin  oil  and 
xylol.  After  this  has  cleared  the  heavier  stain  from  the  section  the 
cigarette  paper  is  eliminated  by  lifting  it  off  the  slide  and  turning  it 
upside  down  on  to  a  fresh  clean  slide,  the  section  thus  coming  to 
rest  on  the  slide.  Blot  carefully  and  peel  the  cigarette  paper  off, 
leaving  the  section  attached  to  the  slide.  Then  continue  the 
differentiation  with  anilin  oil-xylol,  controlling  under  the  microscope. 

Wash  thoroughly  with  xylol. 

Mount  in  Canada  balsam. 

In  this  method  the  sections  should  be  handled  with  glass  rods, 
especially  in  passing  them  into  and  out  of  the  osmic  and  chromic 
acid  fixative. 

Mallory's  Method. 

Fix  in  Zenker's  fluid  either  primarily  or  after  formalin  fixation 
for  twenty-four  hours. 

Wash  for  twenty-four  hours  in  running  water  and  imbed  in 
celloidin  or  paraffin. 

Cut  sections,  and  treat  them  with  iodine  solution  to  remove  the 
mercury  left  in  the  tissues. 

Wash  thoroughly  in  95  per  cent,  alcohol  to  remove  the  iodine. 

Wash  in  water. 


320  STAINING  METHODS 

Treat  with  J  per  cent,  potassium  permanganate  for  five  to  twenty 
minutes. 

Wash  in  water. 

Treat  with  5  per  cent.  oxaHc  acid  five  to  twenty  minutes. 

Wash  thoroughly  in  several  changes  of  water. 

Stain  in  phosphotungstic  acid  haematoxylin  for  twelve  to  twent}^- 
four  hours. 

Haematoxylin      ..          ..          ..          ..  ..  o-i  c.c. 

Water        . .          . .          . .          . .          .  .  .  .  80  c.c. 

10  per  cent,  solution  phosphotungstic  acid  . .  20  c.c. 

Hydrogen  peroxide  (U.S.  Ph.). .          ..  ..  0-2  c.c. 

Transfer  directly  to  95  per  cent,  alcohol,  and  dehydrate  rapidly 
with  absolute  alcohol.     Clear  in  xylol  and  mount  in  Canada  balsam. 

This  method  is  apphcable  to  all  nervous  tissues  fixed  in  Zenker's 
fluid,  which  it  is  thus  possible  to  stain  for  nerve  cells  and  by  ordinary 
tissue  stains,  as  well  as  for  neuroglia  fibres. 

To  stain  the  neuroglia  cell  bodies  various  methods  have  been 
devised.  Alzheimer  has  adopted  special  methods  to  give  differential 
staining  of  the  inclusions  in  these  cells,  but  they  offer  no  advantages 
over  more  simple  methods  for  demonstrating  the  outlines  of  the 
cell  body  and  its  larger  processes.  The  best  of  these  is  Heidenhain's 
iron  alum  haematoxylin  method. 

Ramon-y-Cajal' s  Silver  Method. 

Fix  small  pieces  of  brain  or  cord  in — 

Formol  . .         . .  '      . .         . .         . .       70  c.c. 

Ammon.  bromide      ..  ..  ..  ..       10  grammes. 

Water  . .  . .  . .  . .  . .     430  c.c. 

The  pieces  remain  in  this  for  four  to  five  weeks. 

Cut  at  15  to  20  /^  on  the  freezing  microtome. 

Put  the  sections  in  formol-ammonium  bromide  solution  in  the 
paraffin  oven  at  50°  to  55°  C.  for  ten  to  fifteen  minutes. 

Wash  rapidly  in  plenty  of  water  to  clear  them  of  formol. 

Transfer  to  an  ammoniacal  silver  carbonate  solution  at  50°  to 
55°  C.  until  they  take  on  a  deep  brown  colour.  This  solution  is 
made  by  adding  to  10  c.c.  10  per  cent,  silver  nitrate,  30  c.c.  of  a 
5  per  cent,  solution  of  sodium  carbonate,  dissolving  the  precipitate 
in  strong  ammonia  and  adding  distilled  water  to  150  c.c. 

Wash  rapidly  in  distilled  water,  and  transfer  to  20  per  cent, 
formol  for  one  minute.  Wash  again  in  water,  tone  in  weak  gold 
solution,  fix  in  hyposulphite,  wash,  dehydrate,  clear,  and  mount 
as  in  Bielschowsky's  method  for  frozen  sections. 


APPENDIX  I  321 


REFERENCES 

Walker  Hall  and  Herxheimer:  Methods  of  Morbid  Histology  and  Clinical 
Pathology.     Edinburgh,  1905. 

Mallory  and  Wright:  Pathological  Technique.  Seventh  edition.  Phila- 
delphia, 1918. 

RoussY  AND  Lhermitte:  Les  techniques  anatomo-pathologiques  du  syst^me 
nerveux.     Paris,  1914. 

Spielmeyer,  W.:  Technik  der  Mikroscopischen  Untersuchung  des  N erven- 
systems.     2  Aiif.     Berlin,  1914. 


21 


APPENDIX  II. 

METHODS  OF  EXAMINATION  OF  THE  CEREBRO- 
SPINAL FLUID 

Cell  examination. — This  is  best  done  by  means  of  a  special  counting 
chamber,  the  most  convenient  being  that  of  Fuchs-Rosenthal. 

The  fluid  is  stained  either  with  a  i  per  cent,  solution  of  toluidin 
blue,  or,  if  it  is  desired  to  dissolve  up  the  red  blood  corpuscles,  with 
a  saturated  solution  of  methyl  violet  in  lo  per  cent,  acetic  acid. 
This  stain  is  sucked  up  to  the  mark  i  of  a  Thoma  leucocyte  pipette, 
and  cerebro-spinal  fluid  sucked  up  after  it  to  the  mark  ii.  A  better 
method  when  a  number  of  fluids  are  to  be  examined  is  to  put 
0-45  c.c.  of  cerebro-spinal  fluid  in  a  small  clean  test-tube,  and  to 
add  0*05  c.c.  of  the  stain.  In  either  case  the  stain  is  allowed  to  act 
for  ten  to  fifteen  minutes  before  the  counting  chamber  is  fiUed. 

The  depth  of  the  Fuchs-Rosenthal  chamber  is  y%  mm.,  and 
the  diameter  of  the  squared  area  4  mm.  The  fluid  over  this  area  is, 
therefore,  -V-  c.mm.  As  the  fluid  is  diluted  9  in  10,  the  total 
number  of  cells  counted  within  the  outer  lines  of  the  square  re- 
presents the  number  in  V  XyV  =  "Vir  c.mm.  of  cerebro-spinal  fluid. 
For  practical  purposes  dividing  the  total  number  of  cells  counted 
by  3  gives  the  number  in  i  c.mm.  of  the  fluid. 

It  is  also  possible  to  use  a  Thoma  counting  chamber  by  counting 
fields  after  the  method  of  Strong.  The  field  is  adjusted  by  altering 
the  tube  length  until  its  diameter  corresponds  exactly  with  10  of 
the  small  squares  of  the  ruling.  Each  field  will  then  be  almost 
exactly  \  sq.  mm.  in  area.  As  the  cell  is  ^^  mm.  deep,  by 
counting  50  fields  we  get  the  number  of  cells  in  i  c.mm.  of  diluted 
fluid. 

To  get  a  more  exact  picture  of  the  individual  cells  Quincke's 
original  technique  may  be  employed:  5  to  10  c.c.  of  fluid  are  centri- 
fugalised;  the  fluid  is  poured  out,  and  the  cells  adhering  to  the 
bottom  of  the  tube  are  scraped  off  with  a  capillary  glass  pipette  up 
which  the  fluid  remaining  in  the  tube  runs.  This  is  blown  on  to  a 
clean  albuminised  slide,  dried,  fixed  in  alcohol,  and  stained  by 
Giemsa's  or  Pappenheim's  stains,  or  with  toluidin  blue. 

322 


EXAMINATION  OF  CEREBRO-SPINAL  FLUID     323 

Alzheimer's  method  may  be  used,  but  is  rather  cumbersome. 
He  mixes  the  cerebro-spinal  fluid  with  four  times  its  volimie  of 
absolute  alcohol.  The  resulting  precipitate,  which  contains  the 
albumen  and  cells,  is  centrifugalised ;  the  supernatant  fluid  is  poured 
off,  absolute  alcohol  added,  and  the  tube  centrifugalised  again. 
The  resulting  deposit,  which  is  now  a  firm  mass,  is  imbedded  in 
celloidin,  cut,  and  stained  by  any  methods  applicable  to  celloidin 
sections. 

Methods  of  albumen  examination.  —Where  large  quantities  of  fluid 
are  available,  it  is  possible  to  use  Esbach's,  Sicard's,  or  Aufrecht's 
sedimentation  tubes.  These,  however,  are  not  exact  for  small 
percentages  of  albumen,  such  as  are  normally  found.  Much  better 
is  Mestrezat's  method  of  comparing  the  precipitate  given  by  boiling 
with  trichloracetic  acid,  with  a  standard  scale  of  tubes  containing 
known  quantities  of  albumen.  This  is  made  by  measuring  exactly 
the  amount  of  albumen,  either  in  a  highly  albuminous  cerebro-spinal 
fluid  or  in  a  dilution  of  blood  serum.  A  number  of  narrow  test- 
tubes  of  equal  calibre  are  then  taken,  and  into  each  is  put  2  c.c.  of 
albuminous  fluid  in  strengths  varying  from  o-i  per  cent,  to  o-oi  per 
cent. :  o  -3  c.c.  of  30  per  cent,  trichloracetic  acid  is  added  to  each  tube, 
and  these  are  boiled  and  then  closed  off  in  the  blowpipe  and 
sterilised  at  56°  C.  For  examination  2  c.c.  of  the  cerebro-spinal 
fluid  to  be  tested  are  put  into  a  test-tube  of  similar  calibre,  and 
trichloracetic  acid  added  as  before.  The  tube  is  boiled  and  left  for 
half  an  hour  to  allow  the  precipitate  to  become  flocculent,  and  is 
then  compared  with  the  "  standard  scale."  This  can  be  done  with 
great  exactness  by  noting  which  of  Jaeger's  test  types  can  be  read 
through  the  fluid  in  the  tubes. 

Globulin  estimation — (i)  Nonne-Apelt  reaction  (phase  !).• — Add 
to  I  c.c.  of  cerebro-spinal  fluid  i  c.c.  of  saturated  ammonium  sulphate 
solution.  Shake  the  tube.  The  appearance  of  a  definite  faint 
opalescence,  within  three  minutes  after  mixture  of  the  fluids,  is 
considered  a  weak  positive  reaction.  A  milky  turbidity  constitutes 
a  strong  positive  reaction. 

(2)  Noguchi  {butyric  acid)  reaction. — To  0-2  c.c.  of  cerebro-spinal 
fluid  in  a  test-tube  is  added  0-5  c.c.  of  10  per  cent,  butyric  acid  in 
normal  saline.  The  mixture  is  boiled,  o  -i  c.c.  of  normal  caustic  soda 
added,  and  the  mixture  boiled  again  for  a  few  seconds.  The 
appearance  of  a  granular  or  flocculent  deposit  which  commences  to 
settle  into  a  peUicle  at  the  bottom  of  the  tube  within  three  hours 
constitutes  a  positive  reaction. 

Glucose  estimation. — For  rough  practical  work  the  reduction  of 
Fehling's  solution  may  be  used.    Normally  i  c.c.  of  cerebro-spinal 


324     EXAMINATION  OF  CEREBRO-SPINAL  FLUID 

fluid  reduces  almost  completely  0-25  c.c.  of  mixed  Fehling's  solution, 
giving  a  heavy  red  precipitate  with  a  faint  blue  colour  in  the  super- 
natant fluid.  For  quantitative  estimation  the  only  satisfactory 
methods  are  those  devised  for  blood  analysis.  Of  these  probably 
the  best  is  that  of  McLean  (v.  Cole's  Practical  Physiological 
Chemistry) . 

Chlorides. — These  are  estimated  by  titration  with  standard  silver 
nitrate,  using  potassium  chromate  as  an  indicator.  The  silver 
nitrate  solution  used  contains  5-814  grammes  AgNOg  to  the  litre; 
2  c.c.  of  cerebro-spinal  fluid  are  put  into  about  10  c.c.  of  distilled 
water,  a  few  drops  of  potassium  chromate  solution  added,  and  a 
pinch  of  pure  calcium  carbonate  to  insure  alkalinity.  Silver  nitrate 
is  run  in  out  of  a  burette  until  the  lemon  yellow  colour  changes  to 
orange.  Each  c.c.  of  silver  solution  used  will  then  indicate  i  part 
per  thousand  of  chlorides  in  the  cerebro-spinal  fluid. 

Urea. — This  may  be  estimated  by  any  of  the  hypobromite  methods 
in  common  use.  If  possible,  5  c.c.  of  cerebro-spinal  fluid  should  be 
used.  Or  Kennaway's  soy-bean  method  may  be  used  {v.  Brit. 
Journ.  of  Exper.  Path.,  vol.  i.  (1920),  p.  135). 

Organic  acids. — These  may  be  roughly  estimated  by  Kopetsky's 
method.      A   standardised  Uffelmann's  reagent    is    prepared    by. 
taking — ■ 

5  per  cent,  ferric  chloride         . .  . .  . .         i  part. 

I  per  cent,  carbolic  acid  . .  . .  . .         5  parts. 

Mix.     Take  6  drops. 

Cerebro-spinal  fluid  is  added  drop  by  drop  to  this  until  the  purple 
colour  becomes  yellow.  If  this  appears  on  i  to  3  drops  it 
indicates  great  excess  of  organic  acids;  if  on  3  to  6  drops  it 
indicates  moderate  excess  of  organic  acids;  if  on  6  to  10  drops 
it  indicates  slight  excess  of  organic  acids. 

Reaction  of  Boveri. — One  c.c.  of  cerebro-spinal  fluid  to  be  tested  is 
placed  in  a  small  test-tube.  Allow  i  c.c.  of  o-i  per  cent,  solution  of 
potassium  permanganate  to  run  down  the  side  of  the  tube  on  to  the 
top  of  the  fluid,  taking  care  that  the  fluids  do  not  mix.  A  brownish 
ring  forms  between  the  two  fluids  in  certain  pathological  conditions 
of  the  cerebro-spinal  fluid.  On  mixing  the  fluids  the  colour  of  the 
permanganate  may  be  changed  slightly  or  completely  to  brown. 
A  positive  reaction  is  said  to  indicate  inflammatory  disease  in  the 
cord. 

Lange's  colloidal  gold  reaction. — All  the  water  used  to  make  up 
solutions  for  this  test  must  be  freshly  distilled  twice  in  good  glass, 
using  cork  instead  of  rubber  for  the  connections.    The  glass-ware 


LANGE'S  GOLD-SOL  REACTION 


325 


used  should  be  absolutely  clean.  It  should  be  washed  with 
50  per  cent,  hydrochloric  acid,  washed  out  first  with  tap  and  then 
with  freshly  distilled  water,  and  sterilised  in  the  hot-air  oven  for 
half  an  hour. 

A  litre  of  fresh  double-distilled  water  is  heated  in  a  Jena  glass 
flask  to  60°  C.  Then  add  i  c.c.  of  10  per  cent,  gold  chloride  and 
10  c.c.  of  2  per  cent,  potassium  carbonate  solution.  Shake  well, 
and  heat  rapidly  to  90°  to  95^  C,  not  higher.  Then  take  the  flask 
away  from  the  flame,  and  add  drop  by  drop  with  constant  shaking 
10  c.c.  of  I  per  cent,  formalin  solution.     Stop  as  soon  as  the  solution 

mGR^M  OF  LANGE'S  COLLOIDAL  GOLD  REACTION. 


(After  Miller,  Brush,  Hammers  and  Felton.) 

-  -  -  -      =     MENINGEAL  FIELD 

=    PARETIC  FIELD 

++^.+^.+       =    LUETIC  FIELD 

DILUTIONS 

5 

1 

<55 

1 

1 

<5a 

CM 

i 

5 

COLOURLESS 

4 

PALE  OR 
GREYBLUE 

■ 

rr- 

— i 

J 

BLUE 

^+4 

^\ 

/ 
/ 

\ 
\ 

2 

LILAC  OR 
PURPLE 

*. 
% 

*5 

/ 
/ 
f 

\ 
\ 

\ 

1 

RED 
BLUE 

* 

X 

X 

/ 

/ 
/ 

t 
k 

\ 

',        \ 
•         > 

N 

0 

RED 

X 

+  4--t- 

• 
+  ■».  + 

+ +v 

lv>" 

;v 

~  — 

Fig.  103. 


begins  to  turn  red.  Usually  the  red  colour  develops  rapidly  once  it 
has  commenced.  If  not,  a  few  drops  more  of  formaHn  may  be 
added.  When  cool,  place  in  several  clean,  well-stoppered  flasks  or 
bottles,  and  store  in  a  dark  place.  The  gold  solution  thus  prepared 
should  be  bright  cherry  red  in  colour,  with  no  fluorescence  when 
viewed  by  reflected  light,  and  perfectly  clear  to  transmitted  light. 
If  there  is  any  tendency  to  purple  or  "  old  rose  "  shades,  or  more 
than  the  slightest  degree  of  fluorescence,  it  should  be  discarded. 
The  final  test  of  the  gold  solution  is  that  it  gives  a  curve  of  the 
"  paretic  type,"  with  a  known  sample  of  fluid  from  a  case  of  general 
paralysis. 


326  LANGE'S  GOLD-SOL  REACTION 

For  each  test,  ten  clean  test-tubes  are  set  out  in  a  rack,  and 
another  one  or  two  tubes  are  set  out  for  a  control. 

Into  the  first  tube  of  each  test  0-9  c.c.  of  0-4  per  cent,  saline  is 
put,  and  0-5  c.c.  into  each  of  the  other  tubes  of  the  test  and  the 
controls. 

With  a  clean  dry  pipette  o-i  c.c.  of  the  cerebro-spinal  fluid  to 
be  tested  is  put  into  the  first  tube  of  the  test.  Mix  and  take  up 
0'5  c.c,  which  is  put  into  the  second  tube.  Mix  and  take  up  0-5  c.c. 
and  transfer  it  to  the  third  tube,  and  so  on,  until  the  tenth  tube  of 
the  test  is  reached.  From  this  take  out  0-5  c.c.  of  fluid  and  throw 
it  away. 

Then  to  every  tube  including  the  controls  add  2-5  c.c.  of  the 
colloidal  gold  solution.  Shake  and  leave  at  the  temperature  of  the 
laboratory  for  twelve  to  twenty-four  hours.  Then  read  each  tube 
from  the  i  in  10  dilution  in  order  up  to  the  i  in  5,120  dilution,  giving 
each  degree  of  alteration  in  colour  a  number  from  o  (no  change)  up 
to  5  (complete  loss  of  colour  in  the  tube  except  for  a  bluish 
precipitate) . 

The  curve  of  progressive  general  paral37sis  will  thus  read  some- 
thing like  5.5.5.5.5.4.3.2.1.0  (fig.  103). 


INDEX 

Numbers  in  heavy  type  refer  to  illustrations. 


Abiotrophy,  i 

Abscess  of  the  brain,  24,  85,  163,  179, 
181, 183 

—  of  the  spinal  cord,  184 

— •  after  wounds  of  the  brain    85 
Acetone  in  cerebro-spinal  fluid,  37 
Achromatosis,  6 
Acidosis,  Effects  on  vasomotor  centre, 

81 
Acoustic   nerve   tumours,    247,  243, 

249 
Acromegaly,  256 

—  and  syringomyelia,  290 
Actinomycosis,  163 
Acute  leptomeningitis,  171 

Cerebro-spinal  fluid  in,  39 

Acute  myelitis,  184 

Cerebro-spinal  fluid  below  level 

ot  45 

Acute  poliomyelitis,  193,  195 

Addison's  disease  causing  disease  in 
spinal  cord,  24 

Adventitial  lymph  spaces,  27,  34 

Agenesis,  i 

Albumen  examination  in  cerebro- 
spinal fluid,  323 

Albumoses,  Bence- Jones',  266 

—  in  cerebro-spinal  fluid,  44 
Alcohol  in  cerebro-spinal  fluid,  37 

—  in  relation  to  tabes  dorsalis,  147 
Alcoholic  insanity,  227 

—  neuritis,  223 

Alzheimer's  method  of  cell  examina-   ' 
tion  in  cerebro-spinal  fluid,  323 

Amaurotic  family  idiocy,  58,  60  i 

Amnesia  in  concussion  of  the  brain, 
82  I 

Amyotonia  congenita,  78  j 

Amyotrophic   lateral   sclerosis,    271,    1 
273,  275 

Anaemia  in  subacute  combined  de- 
generation, 277,  282  I 

Anencephaly,  50 

Aneurysm  of  cerebral  arteries,  120, 
259 


Angeioma,  249 

Aniline    poisoning    causing    neuritis, 

223 
Anterior  horns.     See  Ventral  horns 
—  roots.     See  Ventral  roots 
Anthrax  meningitis,  1 75 
Aortitis,  Syphilitic,  in  tabes  dorsalis, 

153 
Arachnoid  cysts,  259 

■  Cerebro-spinal  fluid  below,  44 

Argyll- Robertson  pupil,  152 

—  in  hypertrophic  interstitial 

neuritis,  72 
Arsenical  neuritis,  223 
Arteritis  syphilitica,  138 
Ascending  neuritis  after  injury,  97 
Asphalter's  drop-foot,  102 
Atrophic  sclerosis,  52 
Atrophy  of  brain.  Localised,  52 
Auditory  nerve.  Injuries  of,  94 

Tumours  of.  247,  248,  249 

Aufrecht's  albumino meter,  323 
Axis  cylinders  in  cord.  Changes  due 

to  concussion,  89 

Bandelette  of  Pierret  in  tabes  dor- 
salis, 150 

Basilar  artery.  Atheroma  of,  107 

Bell's  paralysis,  18,  100 

Bence- Jones'  albumoses,  266 

Beri-beri,  234 

Betz  cells  in  chronic  lead  poisoning, 
228 

after  lesions  of  the  pyramidal 

tract,  10 

in  motor  neuron  disease,  274 

Bielschowsky's  method  for  neuro- 
fibrils 4,  49,  225,  305,  310 

Birth  injuries,  58 

Bisulphide  of  carbon  neuritis,  223 

Blood  stream,  Infection  by,  24 

Blood  vessels  in  central  nervous  sys- 
tem. Structure  of,  27 

Bosses  on  skull  in  endothelioma,  253 

Boveri  reaction,  324 


327 


328      PATHOLOGY  OF  THE  NERVOUS  SYSTEM 


Brachial  plexus,  Injuries  to,  loo 
Brain,  Abscess  of,  24,  85,  163,   179, 
181,  183 

—  Injuries  to,  81 
Bronchiectasis  causing  abscess  of  the 

brain,  24,  179 
Brown- Sequard  paralysis  in  syphilitic 

myelitis,  145 
Bulbar  nuclei  in  bulbar  palsy,  273 

—  palsy,  271 

Busch's     modij&cation      of      March  i 
method,  315 

Caisson  disease,  93 

Cajal's  method  for  neuro-fibrils,  305, 

309 

for  neuroglia,  320 

Cancer  of  spine,  264 

• and  herpes  zoster,  213 

—  and  subacute  combined  degenera- 
tion, 282 

Carbol- xylol,  307 

Carbon-monoxide  poisoning  causing 
neuritis,  223 

affecting  the  brain,  228 

Carcinoma  of  brain,  249,  260 

• —  of  vertebrae,  264 

Carotid    artery.    Changes    following 

ligature  of,  13 
Cauda  equina,  Neuro-fibromatosis  of, 

268 
Cavities    in    cord     due    to     pachy- 
meningitis, 137 
Cell    changes    after    lesions    of    axis 

cylinders,  6 
Celloidin     method     for     imbedding 

nervous  tissues,  306 
Cells  in  cerebro-spinal  fluid,  38 

Examination  of,  322 

Central  canal  of  cord,  18 

—  Development  of,  291 

Cerebello-pontine  angle.  Tumours  in, 

247 
Cerebral  abscess,  24,  85,  163,  179 
due  to  streptothrix,  163 

—  asymmetry,  52,  54 

—  embohsm,  105,  106, 112 
and  chorea,  215 

—  haemorrhage,  117,  119 

—  syphilis,  133,  135 

Cerebro-spinal  fluid  in,  41 

Cerebro-spinal  fluid,  30 

in  acute  poliomyelitis,  202 

Amount  of,  33 

Cells  in,  38 

Changes  in  appearance,  37 

—  —  Circulation  of,  31 
Examination  of,  322 

—  —  Function  of,  35 

in  lethargic  encephalitis,  203 

Mode  of  absorption,  33 


Cerebro-spinal  fluid.  Mode  of  forma- 
tion. 30 
Normal  composition  of,  35 

—  —  Pathological  alterations  in,  36 
in  Pott's  disease,  165 

Pressure  of,  ^^ 

in  trypanosomiasis,  217 

Cervical  form  of  tabes  dorsalis,  146 

—  ribs,  loi 
Charcot  joints,  153 
Charcot-Marie  Tooth  paralysis.  70 
Chlorides  in  cerebro-spinal  fluid,  43 

—  ■ —  —  Examination  of,  324 
Chlorosis,  Sinus  thrombosis  in,  124 
Cholesteatoma,  256 

Chorea,  214 

—  Progressive  familial  (Hunting- 
ton's), 68 

Choroid  plexus,  30 

—  ■ —  Failure  of,  42 

Tumours  of,  249 

Chromatolysis,  6,  12 

—  Time  relations  of,  6,  7,  9 
Chromophobe  struma  of  pituitary,  256 
Circulatory  disturbances  of  brain,  103 

Effect  of,  on  nerve  cell,  1 3 

Circumflex  nerve  injuries,  10 1 
Cirrhosis     of     liver     in     progressive 

lenticular  degeneration,  68 
Cisterns  at  base  of  brain.  Function 

of.  82 
Clarke's  column,  10,  199,  210,  232,  282 
Clawhand  in  peroneal  atrophy,  70 
Clubfoot  in  peroneal  atrophy,  70 
Colloid  formation  by  pituitary  gland, 

256,  259 
Colloidal   gold   reaction   in   cerebro- 
spinal fluid,  47,  324,  325 
Comma  tract  in  tabes  dorsalis,  149 
Compound   granular   corpuscles,    28, 

89,  no,  143,  183 
Compression  of  spinal  cord,  269 
Concussion  of  brain,  82 

—  of  the  spinal  cord,  88 
Contrecoup   effect  in   concussion   of 

the  brain,  8^ 
Convolutions,  Foetal  type  of,  52,  53 

—  Parchment-like,  52 
Corpora  amylacea,  23,  24 

in  subacute  combined  degenera- 
tion, 282 

Corps  granuleux.  See  Compound 
granular  corpuscles 

Corpus  callosum.  Degeneration  in 
motor  neuron  disease.  274 

—  striatum.  Lesions  of,  in  paralysis 
agitans,  298 

Cranial  nerves.  Injuries  to,  100 

Lesions    of,     in    disseminated 

sclerosis,  288 
in  syphilitic  meningitis,  136 


INDEX 


329 


Cranial    nerve     palsy     in     cerebral 

tumour,  262 
Cranio-cleido-dysostosis,  52 
Cranium,  Tuberculosis  of,  164 
Crutch  paralysis,  loi 
Cyclencephaly,  51 
Cylindrical    cavities    in    the    spinal 

cord,  88 
Cylindroma,  252,  263 
Cysticerci,  259 
Cysts  of  brain,  258 

—  Dermoid,  256,  268 

—  Parasitic,  259 

Da    Fano's    modification    of    Biels- 

chowsky's  staining  method,  310 
Dejerine-Sottas'  disease,  71 
Dementia  in  Huntington's  chorea,  69 
Dendrites,  Swellings  of,  in  amaurotic 

family  idiocy,  59 
Dermoid  cysts  as  cerebral  tumours, 

256,  268 
Developmental  disease,  50 
Development  of  canal  of  spinal  cord, 

291 
Diabetes,  Cerebro-spinal  fluid  in,  37 
Diffuse  infarction  of  brain,  86 
Dinitro-benzol  neuritis,  223 
Diphtheritic  neuritis,  2,  223 
Diplococci  in  Landry's  paralysis,  209 
Diplococcus  rheumaticus,  214 
Dislocation  of  vertebrae,  91 
Disseminated  sclerosis,  283,  286,  287 
— ;  —  Cerebro-spinal  fluid  in,  39 
Dissociative  anaesthesia  in  haemato- 

myelia,  127 
Disuse  of  nerve  cells,  2 
Dorsal  root  degeneration  in  cerebral 
tumour,  263 

in  herpes  zoster,  213 

in  tabes  dorsalis,  147 

Dorsal  root  ganglia  in  beri-beri,  236 

in  herpes  zoster,  213 

in  leprosy,  162 

in  tabes  dorsalis,  152 

Double  hemiplegia.  Chronic  progres- 
sive, 105 

Echinococcus  cysts,  259 
Electrical     changes     in     muscle     in 
family  periodic  paralysis,  73 

—  —  in  myasthenia  gravis,  300 
in  myotonia,  74 

Embolism  of  cerebral  arteries,    105, 

106,  112 
Encephalitis  lethargica,  202,  204-206, 

208 

—  Suppurative,  179,  181 

—  Tubercular,  169 

—  in  wounds  of  the  brain,  S$ 
Encephalopathy,  227 


End-bulbs  on  injured  nerves,  15,  17, 

97 
Endocarditis  and  chorea,  214 
Endothelioma  of  the  brain,  253,  254, 
266 
j   —  of  the  spinal  meninges,  267 
I    Ependyma,  Origin  of,  18 
;    Ependymal  glioma,  246 
I   Epilepsy  (Jacksonian)  after  injuries 

^  to  the  brain,  ?>t, 
!   Epileptic  convulsions  from  cerebral 
'        anaemia,  104 
Erb-Duchenne  paralysis,  100 
Erb's  syphilitic  paraplegia,  145 

—  type  of  myopathy,  77 
Ergotism,  229 
Exencephaly,  50 

Exogenous  fibres  of  spinal  cord   in 
i       tabes  dorsalis,  149 
j   External  popliteal  nerve  injuries,  loi 
I    Extradural  haemorrhage,  123 
;   —  spinal  tumours,  266 

I   Facial  herpes.  Causation  of,  26 
;   —  paralysis  in  tetanus,  192 

False  porencephaly,  121 
:   Falx  cerebri.  Function  of,  82 

i Endothelioma  of,  264 

.  Famihal  cerebral  degeneration  with 
macular  changes,  61 

—  hypertrophic  neuritis,  71 

—  periodic  paralysis,  73 

Fat  granule  cells.      See  Compound 
granular  corpuscles 

I   —  Stains  for,  316 

'    Fibrin    in    cerebro-spinal    fluid,    37, 
40,  41,  44 

!    Fibro-glioma,  248 

■    Fixation  of  nervous  tissues,  305 

'   Fluorchrome  as  mordant,  312,  317 
Foetal  type  of  convolutions,  52 
Foramina  of  Magendie  and  Luschka, 

31 
Foreign  bodies  in  the  brain,  86,  180 
Formaldehyde  in  the  cerebro-spinal 

fluid,  37 
Formalin-saline  fixation,  306 
"  Four   reactions "   in   the   cerebro- 
spinal fluid,  46 
Fracture  of  the  skull,  84,  100 

—  of  the  vertebrae,  91,  92 
Fxiedreich's  ataxia,  63,  66 
Froin,  Syndrome  of,  38,  43,  45 
Fuchs- Rosenthal  counting  chamber, 

322 

Ganglion  cells.     See  Nerve  cells 
Ganglio -neuroma,  246,  247 
Gas  gangrene  of  the  brain,  85 
Gasserian  ganglion  in  herpes  zoster, 
213 


330       PATHOLOGY  OF  THE  NERVOUS  SYSTEM 

Gasserian  ganglion  in  leprosy,  i6i 
General  paralysis  of  the  insane,  ^5, 

i54>  166,  157 
Cerebro-spinal  fluid  in,  39, 

46,  47 
Gennari,  Fibres  of,  59 
Gitterzell.     See  Compound  granular 

corpuscles 
Glia.     See  Neuroglia 
"  Gliabeize,"  317 
Glial  cells.  Fibre-forming,  56 
Glioma,  240,  241-245 
Gliomatosis  and  syringomyelia,  292 
Gliosis  in  Friedreich's  ataxia,  64 

—  in  progressive  lenticular  degenera- 
tion, 67 

Globulin  in  cerebro-spinal  fluid,  41, 

323 
Glucose  in   cerebro-spinal  fluid,    36, 

42,  323 
Glycerin  gelatin,  317  , 
Gold-Sol  reaction  of  Lange,  47,  324, 

325 
Granular     cells.       See     Compound 

granular  corpuscles 
Gummata,  133,  240 

—  of  spinal  cord,  267 
Gummatous  arteritis,  138,  139,  140 

—  meningitis,  134,  135 
Gutter  fracture  of  skull,  84 


Haematomyelia,  125 
Haematorrhachis,  127 
Haemorrhage,  Extradural,  123 

—  into  areas  of  softening,  83 

—  into  brain,  117,  119 

—  into  dorsal  root  ganglia,  213 

—  into  ventricles,  118 

—  Subarachnoid,  82,  122 

—  Subdural,  122 
Hemisection  of  spinal  cord,  91 
Herpes  zoster,  212 

— •  —  Cerebro-spinal  fluid  in,  39 

His,  Perivascular  space  of,  34 

■ in  lethargic  encephalitis, 

207 
Huntington's  chorea,  68 
-Hyaline  degeneration   of   muscle  in 

myopathy,  77 
Hydatid  cysts  of  the  brain,  259 

of  the  spine,  266 

Hydrocele  of  the  fourth  ventricle,  58 
Hydrocephalus,  Causation  of,  47 

—  from  cerebral  tumour,  260,  261 

—  after  concussion  of  the  brain,  83 

—  External,  52,  57 

—  Internal,  57 

—  in  acute  meningitis,  1 72 

—  in  syphilitic  meningitis,  136 

—  in  tubercular  meningitis,  168 
Hydromyelus,  57,  58 


Hydrophobia,  217 
Hyperactivity  of  cells,  2 
Hyperpyrexia,  Effect  on  nerve  cells, 

13 
Hypertrophic  interstitial  neuritis  of 

children,  71 
— ■  tuberous  sclerosis,  56 
Hypopituitarism  in  cerebral  tumour, 
[        262 

Icterus  neonatorum.  Relation  to  pro- 
j        gressive  lenticular  degeneration,  68 
!   Idiocy,  Amaurotic  family,  58 
!   Infarction  of  brain,  86,  no 

in  lethargic  encephalitis,  203 

Infection  by  blood  stream,  24 
I    Inflammatory    reaction    in     central 

nervous  system,  27 
I    Injuries  to  the  brain,  81 
I  —  to  nerves,  94.  95,  98,  98,  99 

—  to  the  spinal  cord,  87 

—  to  spine  and  herpes  zoster,  213 
Intermedio-lateral  columns,  11 
Interstitial  neuritis,  71,  224 
Intoxication  of  nerve  cells,  2 
Intramedullary  haemorrhage,  125 

i   —  tumours  of  spinal  cord,  267 
i   Intraventricular  haemorrhage,  38 
I    Iodides  in  cerebro-spinal  fluid,  31 

Ischaemia,  2 
I   Ischaemic  softening  of  brain,  105 

I  Jacksonian   fits  after  concussion   of 

j  the  brain,  83 

I  Jaundice    in    progressive    lenticular 

'  degeneration,  67 

Kaiser's  glycerin  gelatin,  317 
Klumpke  type  of  paralysis,  100 
Kopetsky's  method  of  organic  acid 

estimation,  324 
Kornchenzell.    Se^  Compound  granu- 
lar corpuscles 
Kultschitsky-Pal  method  for  myelin, 

314 
Kypho-scoliosis  in  hypertrophic  fami- 
lial neuritis,  72 

Lacunar  softening  of  the  brain,  114 

Landouzy-Dejerine  type  of  myo- 
pathy, 75 

Landry's  paralysis,  209,  211 

Lange's  gold  reaction,  47,  324,  325 

Lathyrism,  25,  232,  233 

Lead  neuritis,  223 

—  encephalopathy,  228 

Lenticular  degeneration.  Progressive, 
familial,  66 

Lenticulo-striate  arteries  in  cerebral 
haemorrhage,  117 

Leprosy,  160,  162 


INDEX 


331 


Leptomeningitis,  Acute,  171 

—  Syphilitic,  136,  143 

—  Tubercular,  167 

Lethargic  encephaUtis,  202,  204-206, 
208 

Cerebro-spinal  fluid  in,  39 

Lhermitte's  neuroglia  method,  318 
Ligature  of  vessels,  Effect  on  nerve 

cells,  13 
Lipochrome  granules  in  nerve  cells, 
6,  14 

in  amaurotic  family  idiocy,  61 

Lipomata  of  spinal  canal,  266 
Liver    cirrhosis    in    progressive    len- 
ticular degeneration,  68 
Locomotor  ataxia,  145 
Loculation     syndrome     in     cerebro- 
spinal fluid,  38,  43,  45 
Longitudinal  sinus  thrombosis,   124, 

177 
Luschka,  Foramina  of,  31 
Lymphangitis  of  syphilis,  131 
Lymphatics,    Infection    of    nervous 
system  through,  26 

—  Perivascular,  27,  34 
Lymphatic  leukaemia  and  subacute 

combined  degeneration,  282 
Lymphorrhages  in  myasthenia  gravis, 
301,  302 

Magendie,  foramen  of,  31 
Mallory's  neurogha  method,  319 
Marchi  method,  14,  16,  375 
Mastoiditis  causing  abscess  of  brain, 

180 
"  Median  triangle  "  in  tabes  dorsalis 

149 
Melanin  pigment,  14 
Meningeal  haemorrhage,  121 
Meningism;  176 
Meningitis .    See  Leptomeningitis  and 

Pachymeningitis 
Meningitis  from  wounds  of  the  brain, 

35 
of  nose,  86 

—  Gummatous,  135 

—  Post-basic,  173 

—  and  syringomyelia,  293 
Meningocele,  50 
Meningococcal  meningitis,  1 73 
Meningo-myelitis,  Syphilitic,  141 

—  Tubercular,  171 

Mestrezat's  method  of  albumen  esti- 
mation, 323 
Microcephaly,  52,  54 
Microgyria,  52 
Middle  root  zone  in  tabes  dorsalis, 

150 
Monakow's  bundle  in  motor  neuron 

disease,  274 
Motor  neuron  disease,  271 


I   Multiple  sclerosis.     5ee  Disseminated 
sclerosis 

Muscles      in      amyotrophic      lateral 
sclerosis,  275,  276 
i   —  in  myasthenia  gravis,  302 
:   —  in  myopathy,  y^,  77 

Myasthenia  gravis,  299 
I   Myatonia congenita.    5ee  Amyotonia 

»  congenita 

Myelin,  Degeneration  of,  16 

—  destruction,  29 

—  Regeneration     of,    in    peripheral 
!        nerves,  17 

'   — •  Stains  for,  312 
Myelitis,  Acute,  184 

—  ex  neuritide,  223 

—  Infective,  184 

— ■  from  lymphatic  infection,  26 
— ■  Septic,  in  wounds  of  the  cord,  91 

—  Suppurative,  184 
i    —  Syphilitic,  141 

I    —  Toxic,  226 

i   — Transverse,  186 

Myeloma  of  spine,  265 

Myopathy,  75 

Myotonia,  74 

—  atrophica,  75 
Myxo-endothelioma,  252 

;   Myxo-fibroma,  248 

I   Negri  bodies,  218 

I   Negro  lethargy,  216 

j   Nephritis,  Cerebro-spinal  fluid  in,  37 

Nerve  cell,  4,  5,  7,  8 

Changes  after  amputation,  9 

—  —  Changes  due  to  circulatory  dis- 
orders, 13 

Changes  in  exhaustion,  12 

Changes  in  hyperpyrexia,  13 

Changes  in  intoxication,  12 

Coagulative  necrosis  of,  13 

Condition  during  activity,  12 

Condition  during  rest,  12 

Parapyknomorphic  state,  12 

Perinuclear  chromatolysis,  12 

Pigmentary  changes,  14 

Pyknomorphic  state,  12 

—  fibre,  14,  15,  16 

—  grafts,  1 7 

Nerve  sheaths,  in  relation  to  cerebro- 
spinal fluid,  31 
Nerves,  Injuries  of.  94.  95,  96,  98-99 

—  Regeneration  after  injury,  97 
Neuralgia,  224 

Neural  lymphatics  in  tetanus,   189, 

191 
Neurinoma,  248 
Neuritis,  222 

—  Ascending  after  injury,  97 

—  in  beri-beri,  236 

—  in  leprosy,  160 


332      PATHOLOGY  OF  THE  NERVOUS  SYSTEM 


Neuritis,     Progressive    hypertrophic 

interstitial  form  of,  71 
Neuroblastoma,  246 
Neuro-epithelioma  gliomatosum,  246 
Neuro-fibrils,  4,  ii 

—  Outgrowth  of,  in  regeneration  of 
nerves,  15 

—  Reaction      of      intracellular,      to 
lesions  of  axis  cylinders,  1 1 

—  Stains  for,  309 

Neuro- fibroma.      Intracranial,      247, 

248-249 
Neuro-fibromata  of  spinal  roots,  266, 

268 
Neuro-fibromatosis  of  cauda  equina, 

268 
Neuroglia,  Function  of,  19 

—  Origin  of,  18 

—  Overgrowth  of,  2,  20,  22 

—  Powers  of  defence  of,  28 

—  Reaction  of,  23 

—  Stains  for,  317 

Neuroglial  cells,  Amoeboid  forms,  20 

"  Fibre-forming,"  21 

Forms  of,  1 8  , 

Miniature,  20 

Neurokeratin  network  in  beri-beri,  236 

Neurolemma  sheath.     See  Sheath  of 
Schwann 

Neuronophagy,    12,    199,    205,    213,    j 
220,  298  1 

Neuron  theory,  2 

Nissl  granules,  4,  5,  6 

Stains  for,  308 

Nitrates  in  cerebro-spinal  fluid,  31 

Noguchi   reaction   in    cerebro-spinal 
fluid,  323 

Nonne-Apelt    reaction    in    cerebro- 
spinal fluid,  323 

Obersteiner,  Pericellular  space  of,  34 
Obregia's  solution,  313 
Obstetrical  injuries  of  spinal  cord,  126 
Odontoid  process.  Fracture  of,  90 
Oedema  of  the  brain  after  wounds  of 

the  head,  85 
in  lead  encephalopathy, 

228 

—  of  the  spinal  cord  after  injury,  89 
Olfactory     nerves,     in     relation     to 

cerebro-spinal  fluid,  31 

Injuries  to,  94,  100 

Optic  atrophy  in  amaurotic  family 

idiocy,  61 

in  disseminated  sclerosis,  290 

in  general  paralysis,  156 

in  tabes  dorsalis,  152 

—  chiasma,  Pressure  of  tumours  on, 
262 

• —  nerves.  Injuries  to,  100 

—  neuritis  in  cerebral  tumour,  262 


Optic  neuritis  in  disseminated  sclero- 
sis, 290 
Organic  acids  in  cerebro-spinal  fluid, 

43 
Osteo-porosis  in  cerebral  tumour,  262 
Otitis  media,  Pyogenic,  177 

Tubercular,  I64 

Oval     field     of     Flechsig     in     tabes 

dorsalis,  149 

Pachymeningitis  cervicalis  hyper- 
trophica,  136 

—  haemorrhagica  interna,  123 
-in  alcoholic  insanity,  228 

—  Pyogenic,  177 

—  Tubercular,  165 

"  Palisade  "  appearance  in  neuro- 
fibroma, 248,  249 

Pallidal  system  of  cells,  298 

Papilloedema,  263 

Paralysis  agitans,  298 

Parasitic  cysts,  259  : 

Parathyroids  in  myasthenia  gravis, 
300 

Parenchymatous  neuritis,  223 

Parkinson's  disease,  298 

Paths  of  infection  in  the  central 
nervous  system,  24 

Pellagra,  230 

—  Cord  changes  in,  25 
Periodic  paralysis,  Familial,  73 
Peripheral  chromatolysis,  13 

—  nerves,  Rapid  regain  of  function 
of,  18 

—  neuritis,  224 
Perithelioma,  251 

Perivascular  infiltration,  27,  131, 169, 
175,  183,  187,  196,  204,  207,  217, 
220,  269,  289 

—  lymphangitis  in  syphilis,  131,  142, 

—  lymphatic  space,  27,  34 

—  sarcoma,  261 

Pernicious  anaemia,  causing  disease 

of  spinal  cord,  24 
Peroneal  atrophy,  70,  71 
Pes  cavus  in  Friedreich's  ataxia,  66 
Pes     equinovarus     in     hypertrophic 

interstitial  neuritis,  72 
Pes  equinus  in  peroneal  atrophy,  70 
Phenol-xylol,  307 
Pineal  tumours,  258 
Pituitary  body  in  myasthenia  gravis, 

—  symptoms  in  cerebral  tumour,  262 

—  tumours,  256,  267,  269 

Plasma  cells,   28,  39,   133,  135.  15^. 

168,  175,  183,  187,  198,  207 
Poliomyelitis,  Acute,  193 
Cerebro-spinal  fluid  in,  37,  39, 

41 


INDEX 


333 


Polyneuritis,  224 

—  of  beri-beii.  236 

—  Cerebro-spinal  fluid  in,  41 

—  gallinarum,  235 

Pons,  Hypertrophy  of ,  240,  243.  245 
Pontine  thrombosis,  107,  108,  il6 
Porencephaly,  False,  56,  121 

—  True,  51 

Post-basic  meningitis,  173,  174 

Cerebro-spinal  fluid  in,  37 

Posterior  horns.     See  Dorsal  horns 

—  roots.     See  Dorsal  roots 

—  longitudinal     bundle     in     motor 
neuron  disease,  274 

Pott's  disease,  90,  164,  166 

Cerebro-spinal  fluid  in,  44 

and  herpes  zoster,  213 

Prenatal  diseases,  52 
Pressure  cone,  48,  261,  262 

—  on  nerves,  100 

Progressive  dementia  from  cerebral 
anaemia,  104 

—  lenticular  degeneration,  66 

—  muscular  atrophy,  271 

—  spinal    muscular   atrophy    of   in- 
fants, 62 

Psammoma    of    cerebral    meninges, 
247,  256 

—  of  spinafl  meninges,  267 
Pseudo-hypertrophic   form    of    myo- 
pathy, 75,  77 

Pseudo-pofencephaly,  56,  121 
Pyaemia  causing  abscess  of  brain,  179 
Pyknomorphic  state  of  nerve  cell,  7 
Pyogenic  pachymeningitis,  177 

Quincke's  method  of  examining  cells 
in  cerebro-spinal  fluid,  322 

Rabies,  217 

Radiculitis  of  dorsal  roots  in  tabes 

dorsalis,  147 
Ramon-y-Cajal.     See  Cajal 
Red     nucleus.     Changes     in,     after 

lesions  of  Monakow's  bundle,  10 
Regeneration  of  nerves  after  injury, 

97 
Reich's  ir  granules  in  pellagra,  232 
Reparation  of  nerve  cells,  7 
Retinal  changes  in  amaurotic  family 

idiocy,  59,  61 
Rosettes  in  gliomata,  246 
Rosin's  method  for  Nissl  granules,  309 

Sarcoma  of  brain,  250 

—  spinal  meninges,  266,  267 

—  of  vertebrae,  265 
Scharlach  R.  stain  for  fat,  14,  316 
Schwann,   Sheath  of,   in  injuries  to 

nerves,  15,  16 
_  —  , —  in  neuritis,  72,  225 


Schwann,  Sheath  of,  in  neuro-fibro- 

mata,  248 
Sclerosis,  Hypertrophic  tuberous,  56 
Scoliosis  in  Friedreich's  ataxia,  66 
Septicaemia,    causing    cerebral    ab- 

I        scess,  24 

I    Septomarginal  tract  in  tabes  dorsalis, 

i        149 

I    Serous  meningitis,  176 
'    Sheath  of  Schwann.     See  Schwann, 
Sheath  of 

Sicard's  albumen  tube,  323 

Sinus  thrombosis,  Primary,  124 

Secondary,  125,  177 

in  wounds  of  the  brain,  86 

i    Sixth  nerve  palsy  in  cerebral  tumour, 

I        262 

j    Skull  in  general  paralysis,  155 

I   —  in  endotheliomata  of  brain,  253 

I   Sleeping  sickness,  216 

Softenings  of  brain,   108,  109,   112, 
113, 115 

Spider  cells,  20,  21,  23,  158,  245 

Spina  bifida,  51 

Spinal   compression.    Pathology    of, 
269 

Spinal  cord.  Concussion  of,  88 

Injuries  of,  87 

Suspension  of  the,  87 

Wounds  of,  88,  90 

—  ganglia.     See  Dorsal  root  ganglia 

—  tumour,  264 

—  tumour,  Cerebro-spinal  fluid  in,  44 
Spirochaeta  pallida,  130 

in  general  paralysis,  154 

Spirochaetes  in  disseminated  sclerosis, 

284 
Staining  methods,  305 
Streptothrix  infection,  163 

of  wounds  of  the  brain,  86 

Subacute  combined  degeneration  of 

spinal  cord,  24,  277,  279,  281 

•  and  pellagra,  231 

Subarachnoid   haemorrhage,  38,   82, 

122 

—  space,  32 

Subdural  haemorrhage,  91,  122 

—  space,  -^T) 

Sudan  III  stain  for  fat,  316 
Superior  longitudinal  sinus.  Wounds 
of,  86 

Rupture  of,  122 

Thrombosis  of,  177 

Sympathetic  ganglia  in  leprosy,  161 

—  nerve  cells,  Changes  in,  after  lesion 
of  sympathetic  chain,  1 1 

Syndrome  of  Froin,  38,  43 
Syphilis,  130 

—  and  neuritis,  223 

SyphiUtic  aortitis  in  tabes  dorsalis, 
^5Z 


334 


PATHOLOGY  OF  THE  NERVOUS  SYSTEM 


Syphilitic  leptomeningitis,  131,  136 

—  meningitis,  Cerebro-spinal  fluid  in, 

and  syringomyelia,  293 

—  myelitis,  141 

—  pachymeningitis,  134,  136 
Syringobulbia,  295 
Syringomyelia,  2,  290,  294 

—  due  to  pachymeningitis,  137 

Tabes  dorsalis,  145,  151,  157 

Cerebro-spinal  fluid  in,  39,  46 

Tay- Sachs  disease,  58,  60 

Tentorium  cerebelli.  Action  in  in- 
juries to  brain,  82,  83 

Tetanus,  26,  188 

Thomsen's  disease,  74 

Thrombosis  of  cerebral  arteries,  105, 
107, 108, 109, 112 

■ — sinuses,  124,  177 

vessels  in  lethargic  en- 
cephalitis, 203,  208 

Thymus  gland  in  myasthenia  gravis, 
300,  303 

Thyroid  gland  in  myasthenia  gravis, 

303 
and  pituitary  tumour,  256 

Torcular  HerophiH,  Pressure  in,  ^^ 
Tract    degeneration    from    cerebral 

softening,  114 
Transverse  myelitis,  186 
Trauma  of  nervous  system,  81 

—  and  syringomyelia,  292 

—  and  tabes  dorsalis,  146 
Trigeminal  neuralgia,  26,  224 
Trjrpanosomiasis,  216 
Tubercular  arteritis,  169 

—  leptomeningitis,  167 

Cerebro-spinal  fluid  in,  37 

—  meningo-myelitis,  171 
• — pachymeningitis,  165 
Tuberculomata  of   brain,    169,    170, 

240 

—  of  spinal  cord,  170,  267 


Tuberculosis,  163 

Tuberous  sclerosis.  Hypertrophic,  56 

Tumours  of  brain,  239 

General  pathology  of,  260 

—  of  the  pineal  body,  258 

—  of  spine  and  spinal  cord,  264 

—  and  syringomyelia,  297 

—  of  vertebrae,  90,  264 
Typhoid  myelitis,  185 

Ulcerative  endocarditis  causing  cere- 
bral abscess,  24 
Ulnar  nerve  injuries,  loi 
Uraemia,  Cerebro-spinal  fluid  in,  41, 

43 
Urea  in  cerebro-spinal  fluid,  43,  324 

Vagus  neuritis  in  beri-beri,  236 

van  Gieson's  stain,  307 

Vasomotor  mechanism  of  medulla,  81 

Venous  sinuses.  Escape  of  cerebro- 
spinal fluid  into,  33 

Ventricular  haemorrhage,  118 

Vertebrae,  Tuberculosis  of,  164 

Vertebral  tumours,  264 

Virchow-Robin  space.  See  Peri- 
vascular lymphatic  space 

Vitamines  and  beri-beri,  234 

Wallerian    degeneration,   2,    16,    97, 

213 
Wassermann    reaction    in     cerebro- 
spinal fluid,  46,  130 
- — ■  —  in  general  paralysis,  154 

in  tabes  dorsalis,  145 

Weigert-Pal  staining  method,  312 
Weigert's  myelin  method,  312 

—  neuroglia  method,  19,  317 
Weigert's  primary  mordant,  306,  312 
Werdnig- Hoffmann  paralysis,  62 
Wounds  of  brain,  84,  180 


Xanthochromia 
fluid,  38,  43 


of     cerebro-spinal 


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